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The first goal of treatment is to correct dehydration. Fluids are often given through a vein (intravenous fluids) to replace fluids lost in diarrhea.
The next goal is to slow the diarrhea. Some medications can help control diarrhea. Octreotide, which is a human-made form of the natural hormone somatostatin, blocks the action of VIP.
The best chance for a cure is surgery to remove the tumor. If the tumor has not spread to other organs, surgery can often cure the condition.
For metastatic disease, peptide receptor radionuclide therapy (PRRT) can be highly effective. This treatment involves attaching a radionuclide (Lutetium-177 or Yttrium-90) to a somatostatin analogue (octreotate or octreotide). This is a novel way to deliver high doses of beta radiation to kill tumours.
Some people seem to respond to a combination chemo called capecitabine and temozolomide but there is no report that it totally cured people from vipoma.
In people presenting with symptoms compatible with radiation enteropathy, the initial step is to identify what is responsible for causing the symptoms. Management is best with a multidisciplinary team including gastroenterologists, nurses, dietitians, surgeons and others.
Medical treatments include the use of hyperbaric oxygen which has beneficial effects in radiation proctitis or anal damage. Nutritional therapies include treatments directed at specific malabsorptive disorders such as low fat diets and vitamin B12 or vitamin D supplements, together with bile acid sequestrants for bile acid diarrhea and possibly antibiotics for small intestinal bacterial overgrowth. Probiotics have all been suggested as another therapeutic avenue.
Endoscopic therapies including argon plasma coagulation have been used for bleeding telangiectasia in radiation proctitis and at other intestinal sites, although there is a rick of perforation. Sucralfate enemas look promising in proctitis.
Surgical treatment may be needed for intestinal obstruction, fistulae, or perforation, which can happen in more severe cases. These can be fatal if patients present as an emergency, but with improved radiotherapy techniques are now less common.
Optimal treatment usually produces significant improvements in quality of life.
In general, treatment for PanNET encompasses the same array of options as other neuroendocrine tumors, as discussed in that main article. However, there are some specific differences, which are discussed here.
In functioning PanNETs, octreotide is usually recommended prior to biopsy or surgery but is generally avoided in insulinomas to avoid profound hypoglycemia.
PanNETs in MEN1 are often multiple, and thus require different treatment and surveillance strategies.
Some PanNETs are more responsive to chemotherapy than are gastroenteric carcinoid tumors. Several agents have shown activity. In well differentiated PanNETs, chemotherapy is generally reserved for when there are no other treatment options. Combinations of several medicines have been used, such as doxorubicin with streptozocin and fluorouracil (5-FU) and capecitabine with temozolomide. Although marginally effective in well-differentiated PETs, cisplatin with etoposide has some activity in poorly differentiated neuroendocrine cancers (PDNECs), particularly if the PDNEC has an extremely high Ki-67 score of over 50%.
Several targeted therapy agents have been approved in PanNETs by the FDA based on improved progression-free survival (PFS):
- everolimus (Afinitor) is labeled for treatment of progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease. The safety and effectiveness of everolimus in carcinoid tumors have not been established.
- sunitinib (Sutent) is labeled for treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease. Sutent also has approval from the European Commission for the treatment of 'unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors with disease progression in adults'. A phase III study of sunitinib treatment in well differentiated pNET that had worsened within the past 12 months (either advanced or metastatic disease) showed that sunitinib treatment improved progression-free survival (11.4 months vs. 5.5 months), overall survival, and the objective response rate (9.3% vs. 0.0%) when compared with placebo.
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.
Prevention of radiation injury to the small bowel is a key aim of techniques such as brachytherapy, field size, multiple field arrangements, conformal radiotherapy techniques and intensity-modulated radiotherapy. Medications including ACE inhibitors, statins and probiotics have also been studied and reviewed.
For symptomatic relief of carcinoid syndrome:
- Octreotide (a somatostatin analogue which decreases the secretion of serotonin by the tumor and, secondarily, decreases the breakdown product of serotonin (5-HIAA))
- Telotristat ethyl (Xermelo) along with a somatostatin analogue in patients not responding to somatostatin analogue monotherapy. It is a tryptophan hydroxylase inhibitor and reduces the production of serotonin.
- Peptide receptor radionuclide therapy (PRRT) with lutetium-177, yttrium-90 or indium-111 labeled to octreotate is highly effective
- Methysergide maleate (antiserotonin agent but not used because of the serious side effect of retroperitoneal fibrosis)
- Cyproheptadine (an antihistamine drug with antiserotonergic effects)
Alternative treatment for qualifying candidates:
- Surgical resection of tumor and chemotherapy (5-FU and doxorubicin)
- Endovascular, chemoembolization, targeted chemotherapy directly delivered to the liver through special catheters mixed with embolic beads (particles that block blood vessels), used for patients with liver metastases.
In localized, resectable adult GISTs, if anatomically and physiologically feasible, surgery is the primary treatment of choice. Surgery can be potentially curative, but watchful waiting may be considered in small tumors in carefully selected situations. Post-surgical adjuvant treatment may be recommended. Lymph node metastases are rare, and routine removal of lymph nodes is typically not necessary. Laparoscopic surgery, a minimally invasive abdominal surgery using telescopes and specialized instruments, has been shown to be effective for removal of these tumors without needing large incisions. The clinical issues of exact surgical indications for tumor size are controversial. The decision of appropriate laparoscopic surgery is affected by tumor size, location, and growth pattern.
Radiotherapy has not historically been effective for GISTs and GISTs do not respond to most chemotherapy medications, with responses in less than 5%. However, three medications have been identified for clinical benefit in GIST: imatinib, sunitinib, and regorafenib.
Imatinib (Glivec/Gleevec), an orally administered drug initially marketed for chronic myelogenous leukemia based on bcr-abl inhibition, also inhibits both "c-kit" tyrosine kinase mutations and PDGFRA mutations other than D842V, is useful in treating GISTs in several situations. Imatinib has been used in selected neoadjuvant settings. In the adjuvant treatment setting, the majority of GIST tumors are cured by surgery, and do not need adjuvant therapy. However, a substantial proportion of GIST tumors have a high risk of recurrence as estimated by a number of validated risk stratification schemes, and can be considered for adjuvant therapy. The selection criteria underpinning the decision for possible use of imatinib in these settings include a risk assessment based on pathological factors such as tumor size, mitotic rate, and location can be used to predict the risk of recurrence in GIST patients. Tumors <2 cm with a mitotic rate of <5/50 HPF have been shown to have lower risk of recurrence than larger or more aggressive tumors. Following surgical resection of GISTs, adjuvant treatment with imatinib reduces the risk of disease recurrence in higher risk groups. In selected higher risk adjuvant situations, imatinib is recommended for 3 years.
Imatinib was approved for metastatic and unresectable GIST by the US FDA, February 1, 2002. The two-year survival of patients with advanced disease has risen to 75–80% following imatinib treatment.
If resistance to imatinib is encountered, the multiple tyrosine kinase inhibitor sunitinib (marketed as Sutent) can be considered.
The effectiveness of imatinib and sunitinib depend on the genotype. cKIT- and PDGFRA-mutation negative GIST tumors are usually resistant to treatment with imatinib as is neurofibromatosis-1-associated wild-type GIST. A specific subtype of PDGFRA-mutation, D842V, is also insensitive to imatinib.
Regorafenib (Stivarga) was FDA approved in 2013 for advanced GISTs that cannot be surgically removed and that no longer respond to imatinib (Gleevec) and sunitinib (Sutent).
Symptoms of short bowel syndrome are usually addressed with medication. These include:
- Anti-diarrheal medicine (e.g. loperamide, codeine)
- Vitamin, mineral supplements and L-glutamine powder mixed with water
- H2 blocker and proton pump inhibitors to reduce stomach acid
- Lactase supplement (to improve the bloating and diarrhoea associated with lactose intolerance)
In 2004, the USFDA approved a therapy that reduces the frequency and volume of total parenteral nutrition (TPN), comprising: NutreStore (oral solution of glutamine) and Zorbtive (growth hormone, of recombinant DNA origin, for injection) together with a specialized oral diet. In 2012, an advisory panel to the USFDA voted unanimously to approve for treatment of SBS the agent teduglutide, a glucagon-like peptide-2 analog developed by NPS Pharmaceuticals, who intend to market the agent in the United States under the brandname Gattex. Teduglutide had been previously approved for use in Europe and is marketed under the brand Revestive by Nycomed.
Surgical procedures to lengthen dilated bowel include the Bianchi procedure, where the bowel is cut in half and one end is sewn to the other, and a newer procedure called serial transverse enteroplasty (STEP), where the bowel is cut and stapled in a zigzag pattern. Heung Bae Kim, MD, and Tom Jaksic, MD, both of Children's Hospital Boston, devised the STEP procedure in the early 2000s. The procedure lengthens the bowel of children with SBS and may allow children to avoid the need for intestinal transplantation. As of June 2009, Kim and Jaksic have performed 18 STEP procedures. The Bianchi and STEP procedures are usually performed by pediatric surgeons at quaternary hospitals who specialize in small bowel surgery.
Surgical treatment remains the treatment of choice for cats and dogs diagnosed with intestinal tumors who are in otherwise good health.
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.
Even if the tumor has advanced and metastasized, making curative surgery infeasible, surgery often has a role in neuroendocrine cancers for palliation of symptoms and possibly increased lifespan.
Cholecystectomy is recommended if there is a consideration of long-term treatment with somatostatin analogs.
In secretory tumors, somatostatin analogs given subcutaneously or intramuscularly alleviate symptoms by blocking hormone release. A consensus review has reported on the use of somatostatin analogs for GEP-NETs.
These medications may also anatomically stabilize or shrink tumors, as suggested by the PROMID study (Placebo-controlled prospective randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumors): at least in this subset of NETs, average tumor stabilization was 14.3 months compared to 6 months for placebo.
The CLARINET study (a randomized, double-blind, placebo-controlled study on the antiproliferative effects of lanreotide in patients with enteropancreatic neuroendocrine tumors) further demonstrated the antiproliferative potential of lanreotide, a somatostatin analog and recently approved FDA treatment for GEP-NETS. In this study, lanreotide showed a statistically significant improvement in progression-free survival, meeting its primary endpoint. The disease in sixty five percent of patients treated with lanreotide in the study had not progressed or caused death at 96 weeks, the same was true of 33% of patients on placebo. This represented a 53% reduction in risk of disease progression or death with lanreotide based on a hazard ratio of .47.
Lanreotide is the first and only FDA approved antitumor therapy demonstrating a statistically significant progression-free survival benefit in a combined population of patients with GEP-NETS.
Other medications that block particular secretory effects can sometimes relieve symptoms.
Surgery can usually cure VIPomas. However, in one-third to one-half of patients, the tumor has spread by the time of diagnosis and cannot be cured.
Surgical management is reserved for fixing anatomical causes of bowel obstruction that interfere with normal function once they are amenable to such intervention. These conditions include:
- Strictures
- Fistulae
- Diverticula
Stem cell therapy is undergoing research as a possible treatment for IBD. A review of studies suggests a promising role, although there are substantial challenges, including cost and characterization of effects, which limit the current use in clinical practice.
Prucalopride, pyridostigmine, metoclopramide, cisapride, and erythromycin may be used, but they have not been shown to have great efficacy. In such cases, treatment is aimed at managing the complications. Linaclotide is a new drug that received approval from Food and Drug Administration in August 2012 and looks promising in the treatment of chronic intestinal pseudo-obstruction, gastroparesis and inertia coli.
Intestinal stasis, which may lead to bacterial overgrowth and subsequently, diarrhea or malabsorption, is treated with antibiotics.
Nutritional deficiencies are treated by encouraging patients to avoid food high in fat and fibre, which are harder to digest and increase abdominal distention and discomfort, and have small, frequent meals (5–6 per day), focusing on liquids and soft food. Reducing intake of poorly absorbed sugar alcohols may be of benefit. Referral to an accredited dietitian is recommended. If dietary changes are unsuccessful in meeting nutritional requirements and stemming weight loss, enteral nutrition is used. Many patients eventually require parenteral nutrition.
Total parenteral nutrition (TPN) is a form of long-term nutritional treatment needed for patients that have severe pseudoobstruction. After a period of no improvement of intestinal function or motility the decision to start TPN will be made, and the surgical procedure to add a long-term, more permanent IV to administer TPN will occur. Types of IV catheters to be placed will be a PICC line or central line which include mediports, Broviac, or Hickman lines depending on how long the physicians believe the patient will require TPN. Patients that are deemed TPN dependent will require constant checkups to monitor the catheter is working properly, check liver enzyme levels and look for signs of blood infections, as catheter blockage, liver damage, and infections of catheters are the main complications associated with long term TPN use and can result in sepsis and/or additional surgeries if not properly monitored. TPN nutritional feeds are given over a period of several hours to all day infusions, and are a mixture of all the vitamins, minerals, and calories similar to what one would get eating orally daily as well as any other specific nutritional needs the patient has at the moment. TPN format is typically changed depending on loss/gain of weight and bloodwork results, and is specially formulated to meet each individual patient's needs.
Use of octreotide has been described.
Cannabis has long been known to limit or prevent nausea and vomiting from a variety of causes. This has led to extensive investigations that have revealed an important role for cannabinoids and their receptors in the regulation of nausea and emesis. With the discovery of the endocannabinoid system, novel ways to regulate both nausea and vomiting have been discovered that involve the production of endogenous cannabinoids acting centrally. The plant cannabis has been used in clinics for centuries, and has been known to be beneficial in a variety of gastrointestinal diseases, such as emesis, diarrhea, inflammatory bowel disease and intestinal pain. Moreover, modulation of the endogenous cannabinoid system in the gastrointestinal tract may provide a useful therapeutic target for gastrointestinal disorders. While some GI disorders may be controlled by diet and pharmaceutical medications, others are poorly moderated by conventional treatments. Symptoms of GI disorders often include cramping, abdominal pain, inflammation of the lining of the large and/or small intestine, chronic diarrhea, rectal bleeding and weight loss. Patients with these disorders frequently report using cannabis therapeutically.
In a 2012 animal study, cannabichromene was shown to normalize gastrointestinal hypermotility without reducing the transit time. The study notes that this result is of potential clinical interest, as the only drugs available for intestinal dysmotility are often associated with constipation.
The "treat empirically" route also has its difficulties, which have all come under wide debate and study. Recommendations are varied but seem to find some common ground around the notion that treatment should be individualized to the specific circumstances under which a patient has developed BLS since these circumstances affect the complex microbial make up of the affected bowel.
Tetracyclines have been the mainstay of treatment for BLS, but recent studies have concluded Rifaximin to be very effective in the treatment of BLS. One study by Di Stefano et al., however, concluded Metronidazole to be more effective than Rifaximin in the treatment of BLS.
Secondary chronic intestinal pseudo-obstruction is managed by treating the underlying condition.
There is no cure for primary chronic intestinal pseudo-obstruction. It is important that nutrition and hydration is maintained, and pain relief is given. Drugs that increase the propulsive force of the intestines have been tried, as have different types of surgery.
Complementary and alternative medicine approaches have been used in inflammatory bowel disorders. Evidence from controlled studies of these therapies has been reviewed; risk of bias was quite heterogeneous. The best supportive evidence was found for herbal therapy, with Plantago ovata and curcumin in UC maintenance therapy, wormwood in CD, mind/body therapy and self-intervention in UC, and acupuncture in UC and CD.
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.
Other medical treatments have been tried and include estrogen and progesterone therapy, Corticostreoids are effective, but are "limited by their side effects."
For patients who do not adequately respond to dietary fiber, osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose can help avoid "cathartic colon" which has been associated with stimulant laxatives. Among the osmotic laxatives, doses of 17–26 g/d of polyethylene glycol have been well studied. Lubiprostone (Amitiza) is a gastrointestinal agent used for the treatment of idiopathic chronic constipation and constipation-predominant IBS. It is well tolerated in adults, including elderly patients. As of July 20, 2006, lubiprostone had not been studied in pediatric patients. Lubiprostone is a bicyclic fatty acid (prostaglandin E1 derivative) that acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements. Unlike many laxative products, lubiprostone does not show signs of tolerance, dependency, or altered serum electrolyte concentration.
Medications may consist of stool softeners and laxatives in IBS-C and antidiarrheals (e.g., opiate, opioid, or opioid analogs such as loperamide, codeine, diphenoxylate) if diarrhea is predominant.
Drugs affecting serotonin (5-HT) in the intestines can help reduce symptoms. On the other hand, many IBS-D patients report that SSRI type medications exacerbate spasms and diarrhea. This is thought to be due to the large number of serotonin receptors in the gut. 5HT3 antagonists such as ondansetron are effective in postinfectious IBS and diarrhea-dominant IBS due to their blockade of serotonin on 5HT3 receptors in the gut; the reason for their benefit is believed to be that excessive serotonin in the gut is thought to play a role in the pathogenesis of some subtypes of IBS. Certain atypical antipsychotic medications, such as clozapine and olanzapine, may also provide relief due to serotonergic properties these agents possess, acting on the same receptors as other medications in this specific category. Benefits may include reduced diarrhea, reduced abdominal cramps, and improved general well-being. Any nausea present may also respond to 5HT3 antagonists owing to their antiemetic properties. Serotonin stimulates the gut motility and so agonists can help constipation-predominant irritable bowel, while antagonists can help diarrhea-predominant irritable bowel. Selective serotonin reuptake inhibitors, SSRIs, frequently prescribed for panic and/or anxiety disorder and depression, affect serotonin in the gut, as well as the brain. The bowels are highly dependent on serotonin for neural communication. "Selective serotonin reuptake inhibitor antidepressants seem to promote global well-being in some patients with irritable bowel syndrome and, possibly, some improvement in abdominal pain and bowel symptoms, but this effect appears to be independent of improved depression. Further research is required."
Mast cells and the compound that they secrete are central to the pathophysiology and implicated in the treatment of IBS; some of the secreted mast cell mediators (and associated receptors) which have been implicated in symptoms of IBS or specific subtypes include: histamine (HRH1, HRH2, HRH3), tryptase and chymase (PAR2), serotonin (5-HT3), PGD2 (DP1). Histamine also causes epithelial secretion of chloride ions and water (associated with secretory diarrhea) by signaling through a receptor or ligand-gated ion channel that has not been identified as of 2015. A 2015 review noted that both H1-antihistamines and mast cell stabilizers have shown efficacy in reducing pain associated with visceral hypersensitivity in IBS; other lower quality studies have also suggested the benefit of these agents for IBS. In a related review on idiopathic mast cell activation syndromes (including IBS), a combined treatment approach using antileukotrienes, H1/H2-antihistamines, and a mast cell stabilizer are suggested.
GAVE is treated commonly by means of an endoscope, including argon plasma coagulation and electrocautery. Since endoscopy with argon photocoagulation is "usually effective", surgery is "usually not required". Coagulation therapy is well-tolerated but "tends to induce oozing and bleeding." "Endoscopy with thermal ablation" is favored medical treatment because of its low side effects and low mortality, but is "rarely curative." Treatment of GAVE can be categorized into endoscopic, surgical and pharmacologic. Surgical treatment is definitive but it is rarely done nowadays with the variety of treatment options available. Some of the discussed modalities have been used in GAVE patients with another underlying disease rather than SSc; they are included as they may be tried in resistant SSc-GAVE patients. Symptomatic treatment includes iron supplementation and blood transfusion for cases with severe anemia, proton pump inhibitors may ameliorate the background chronic gastritis and minute erosions that commonly co-existed in biopsy reports.
Differentiation of DIOS from constipation is generally performed by unit specializing in the treatment of cystic fibrosis. Adequate hydration and an aggressive regimen of laxatives are essential for treatment and prevention of DIOS. Osmotic laxatives such as polyethylene glycol are preferred. Individuals prone to DIOS tend to be at risk for repeated episodes and often require maintenance therapy with pancreatic enzyme replacement, hydration and laxatives (if the symptoms are also mild).
Oral contrast instillation into the colon/ileum under radiological control has been found to reduce the need for surgical intervention.