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Treatment Options for Ulcerative ColitisKaylee DestitoState University of New York Polytechnic InstituteTreatment Options for Ulcerative Colitis Inflammatory bowel disease affects one million Americans nationwide and is characterized as unpredictable, debilitating illness that includes remission and flare ups CITATION Kem13 \l 1033 (Kemp, Dunn, & Schultz, 2013). There are two types of inflammatory bowel disease (IBD): Crohn’s disease and ulcerative colitis. Ulcerative colitis is a chronic inflammatory disorder of the colon that manifests with classic symptoms of bloody diarrhea and fecal urgency (Gordon, et al., 2016). Ulcerative colitis can be managed pharmacologically or surgically. The goal of pharmacological treatment is to induce and maintain remission CITATION Gor16 \l 1033 (Gordon, et al., 2016). Operations for ulcerative colitis are indicative when perforation, toxic megacolon, hemorrhage, dysplasia or failure with medications occurs CITATION Gel14 \l 1033 (Geltzeiler, et al., 2014). According to the Crohn’s and Colitis Foundation of America [CCFA] (2016), ulcerative colitis only affects the lining of the large intestine (colon). It is a chronic disease where tiny sores, ulcers, develop on the lining of the intestine wall which produce gas and mucus (CCFA, 2016). These ulcers induce recurrent inflammation to the lining which causes abdominal discomfort with frequent emptying of the colon (CCFA, 2016). Ulcerative colitis does not skip any areas of the colon. It usually starts at the rectum and moves proximal (CCFA, 2016). Ulcerative colitis can present in three different severities: mild, moderate or severe (CCFA, 2016). The severity depends on how many bowel movements are occurring daily and if blood or systemic symptoms are present (CCFA, 2016). Ulcerative colitis is thought to be caused by a few different factors but the overall process is a turned on immune system that cannot be turned off (CCFA, 2016). Other causes can be due to inherited genes, which run in families, or an actual antigen. The antigen was present at one point but the immune system still keeps initiating an immune response (CCFA, 2016). The prevalence of ulcerative colitis is roughly 205-240 per 100,000 Americans CITATION Dun15 \l 1033 (Dunphy, Winland-Brown, Porter, & Thomas, 2015). Males and females are equally affected. Risk factors for ulcerative colitis are having a family member with the disease, a non-smoker, and those with Jewish, European or Scandinavian heritage (Dunphy et al., 2015). Those with ulcerative colitis are at an increased risk for colorectal cancer (CCFA, 2016). Colonoscopies play a big role in diagnosis and monitoring of this disease. Repeated colonoscopies every one to two years assess progression of disease as well as monitor for colon cancer (CCFA, 2016). There are multiple ways to treat ulcerative colitis. Treatment is tailored to each individual patient and is not universal CITATION Blo14 \l 1033 (Blonski, Bucher, & Lichtenstein, 2014). There are four different classes of medications to help induce remission. The treatment for mild to moderate ulcerative colitis is oral or topical 5-aminosalicyclic acids which has an anti-inflammatory affect (Cope, 2013). These medications are used for first line treatment and maintenance. If symptoms still persist after remission is achieved (lack of flare ups), corticosteroids are the next medication option (Cope, 2013). Once remission has been achieved, steroids need to be tapered off due to side effects and resistance (Cope, 2013). If symptoms still persist with the use of steroids, immunosuppressive/immunomodulatory medications such as thiopurine are used (Cope, 2013). Examples of thiopurine medications used are Azathiopurine (AZA) and 6-Mercaptopurine (6-MP) (Cope, 2013). Thiopurine medications are indicated for moderate to severe flare ups. The last type of medication indicated for ulcerative colitis is biologic therapy including the drug Infliximab which is a tumor necrosis factor antibody (Cope, 2013). These type of medications are used in severe flare ups (Cope, 2013). There are recommended standards of these classes of medication as to what to start first but cannot always be followed per patient based on compliance, disease severity or side effects. If medications are unable to decrease flare ups, surgery is the next option. The ultimate goal of operation is to remove all disease prone mucosa to achieve a cure CITATION Gel14 \l 1033 (Geltzeiler, et al., 2014). There are two surgical options. A total proctocolectomy is the removal of the entire colon and rectum which is a total cure of ulcerative colitis. A total abdominal colectomy is the surgical removal of the colon. The purpose of this literature review is to highlight research already done on the classes of medications used to treat ulcerative colitis along with surgical approaches. This is to shed light on the treatment options for ulcerative colitis patients. Ulcerative colitis is a chronic disease process that takes a toll not only on the patient’s body but also their quality of life. A provider, such as a family nurse practitioner, needs to be aware of current research and standards for the treating ulcerative colitis. This is because ulcerative colitis involves complex treatment options that a provider cannot apply to all patients with this disease. This is evidenced by the costs of ulcerative colitis treatment. Healthcare expenses for the insurer is up to 610 million dollars with out of pocket costs at 8.6 billion dollars (Gordon, et al., 2016) MethodsArticles were retrieved from the State University of New York Polytechnic library website using various databases. The databases searched were, CINAHL, Cochrane, ALT Healthcare, Medline and Health Source. The search was for research articles on treatments for ulcerative colitis. The searched terms were as follows: ‘treatment of ulcerative colitis’, ‘treatment options AND ulcerative colitis’, ‘ulcerative colitis treatment’, ‘ulcerative colitis AND treatment’, ‘ulcerative colitis’, ‘total colectomy AND ulcerative colitis’, ‘ulcerative colitis AND immunomodulators’ and ‘ulcerative colitis AND anti-TNF’. Inclusion and ExclusionThe review included research articles that focused on treatment options for ulcerative colitis. The articles chosen were within the last five years. The total articles included in this review are nineteen. They are broken down as follows: five articles on surgery options for ulcerative colitis, four articles for TNF/ immunomodulatory medications, two articles included all types of treatment medications, two articles focused on corticosteroids and five articles on 5-ASA medication therapy. The data that was excluded were those that were not research articles, those over five years old, those that did not include any treatment options for ulcerative colitis, those that focused on Crohn’s disease options were excluded. Literature ReviewPharmacologic Treatments 5-ASA. The first line of treatment for mild to moderate ulcerative colitis is the use of 5- aminosalicylic acids CITATION Zha14 \l 1033 (Zhao, Li, Chen, Yuan, & Chen, 2014). 5-ASA medications, specifically, sulfasalazine was initially used to treat inflammatory joint disease but are now used for IBD CITATION Fre12 \l 1033 (Freeman, 2012). Localized proctitis, left-sided colitis, extensive colitis are treated alone with 5-ASA or with a combination therapy CITATION Fre12 \l 1033 (Freeman, 2012). Ninety percent of this type of medication has shown to reach the colon and induce remission in mild to moderate ulcerative colitis CITATION Fre12 \l 1033 (Freeman, 2012). 5-ASA medications include, sulfasalazine, olsalazine, balsalazide and mesalamine with each of these having different kinetic delivery and location of action CITATION Fre12 \l 1033 (Freeman, 2012). There is little evidence out there to show which one is better than the other CITATION Fre12 \l 1033 (Freeman, 2012). Zhao, et al. (2014) conducted a study to see if 5-ASA medications protect against the formation of colorectal cancer. Those with ulcerative colitis are at an increased risk for colorectal cancer. Zhao, et al. (2014) performed a literature review on 5-ASA medications and how these medications can reduce the risk of colorectal neoplasia. Seventeen studies were included in Zhao’s et al. (2014) analysis. All the studies showed an association of reduced risk of neoplasms with the use of 5-ASA medications especially with the use of a high dose 5-ASA (Zhao et al., 2014). Colonoscopy surveillance at regular intervals with biopsies are the most effective way to monitor for this (Zhao et al., 2014). The chronic inflammation is a key factor in the development of neoplasms with other risk factors including, duration of onset, severity extent and degree of histology inflammation (Zhao et al., 2014). Limitations of this study was the lack of information on the dose and frequency in which 5-ASA was taken. Depending on where ulcerative colitis is located, distal or extensive region plays a role in how effective the 5-ASA medication will be (Zhao et al., 2014). Overall, Zhao et al. (2014) found that 5-ASA use was associated with reduced risk of neoplasm for ulcerative colitis patients but a large population base study needs to be performed for better concrete results. The use of 5- ASA are beneficial anti-inflammatory drugs and when given orally can induce remission in mild/moderate ulcerative colitis (Ford et al., 2011). There are three types of dosing for 5-ASA. The high dose is over 2.5mg/kg a day, standard dose is 2-2.5mg/kg a day and a low dose is less than 2mg/kg a day (Ford et al., 2011).. Ford et al.(2011) compared the efficiency of 5-ASA to a placebo to induce remission in a systematic review and meta-analysis. Ford et al.(2011) goes on to state that there are no previous meta-analysis conducted that studied the effects of high dose 5-ASA medications to achieve remission. Thirty seven studies were included in this analysis (Ford et al., 2011). Sulfasalazine, mesalamine and balsalazide were superior when compared to the placebo to reduce remission of active ulcerative colitis in this study (Ford et al., 2011). There was no difference between high dose, standard dose and low dose in achieving remission (Ford et al., 2011). But there was a significant improvement with a dose of 2.0mg/kg or higher a day when compared to a low dose (Ford, et al., 2011). The limitations to this study is the number of articles reviewed. Only 37 articles were reviewed to come to these conclusions which cannot be generalized to all ulcerative colitis patients. A positive to this study is that Ford et al. (2011) only included articles where the results of remission were concluded by endoscopic views instead of objective symptoms. The overall result was that 5-ASA medications are more effective than the placebos to induce remission CITATION For11 \l 1033 (Ford, et al., 2011). The type of medication treatment for ulcerative colitis depends on the extent of the disease whether oral, topical or combined therapy will be chosen (Ford et al., 2011). Ulcerative colitis can affect either the distal area of the colon or move proximal involving the whole colon (Ford et al., 2012). The route of medication depends on what extent of the colon is involved (Ford et al., 2012). Topical medications need to be used for mild to moderate active proctitis (Ford et al., 2012). Proctitis is ulcerative colitis that is only located in the rectum area (Ford et al., 2012). Combined therapies are oral and topical medications which can be used for mild to moderate flare ups of left sided colitis (Ford et al., 2012). Left sided colitis is when the rectum to the descending colon and sigmoid are involved (Ford et al., 2012). Ford et al.(2012) wanted to see the efficacy of oral 5-ASA medications compared to topical and combined therapies by conducting a systematic review and meta-analysis. Overall twelve studies were analyzed. Results concluded that there was no difference to induce remission in active ulcerative colitis between topical and oral 5-ASA (Ford et al., 2012). There was also failure to achieve remission with just oral 5-ASA use (Ford et al., 2012). There was a decrease between flare-ups when both topical and oral medications were used (Ford et al., 2012). Prevention of relapse was seen with topical 5-ASA compared to oral 5-ASA (Ford et al., 2012). The limitations to the Ford, et al. (2012) study was that the quality of studies they found, did not use endoscopic as a way to define remission. Therefore, were the results of true remission or just improvement of symptoms? More detailed research needs to be conducted on the use of topical versus oral medication use. Failure to remain in remission might not only be due to the type or route of medication used but also the non-compliance of the patient. There has been higher relapse rates with oral 5-ASA medications which may be due to noncompliance issues (Ford et al., 2012). Overall results from Ford et al. (2012) showed the benefit in combined therapy of 5-ASA therapy over oral alone to induce remission. There is evidence that intermittent use of topical 5-ASA can prevent flare-ups compared to taking just oral 5-ASA (Ford et al., 2012).One of the first line treatments to induce and maintain remission in ulcerative colitis patients is mesalamine, a type of 5-ASA. (Gordon et al., 2016). Gordon et al. (2016) conducted a phase 3 randomized, double blind, placebo-controlled trial in the United States and in Russia. This study was conducted to see the effectiveness of mesalamine medication compared to a placebo (Gordon et al., 2016). The study was mesalamine 1.5grams daily versus a placebo drug taken once a day for six months (Gordon et al., 2016). There were 257 patients in this study, 154 from Russia and 103 from the United States (Gordon et al., 2016). The results showed that there was a significant number of patients that maintained remission at six months with mesalamine versus the placebo (Gordon et al., 2016). Mesalamine was well tolerated with common side effects including headaches, diarrhea and abdominal pain (Gordon et al., 2016). There was also a higher compliance rate with the once a day dosing (Gordon et al., 2016). Limitations to this study were only mild to moderate ulcerative in remission were included therefore the results could not be applied to those with severe ulcerative colitis (Gordon et al., 2016). Overall, the 1.5gram once a day of mesalamine is effective, well tolerated for maintenance of ulcerative colitis. Corticosteroids. Budesonide is an oral, second generation steroid that in indicated for the use of mild to moderate ulcerative colitis to induce remission by inhibiting the inflammatory processes CITATION Lic16 \l 1033 (Lichtenstein, 2016). If the first line of treatment with 5-ASA have failed, the use of steroids is the next medication in line to be utilized CITATION Lic16 \l 1033 (Lichtenstein, 2016). Standard budesonide is absorbed in the ileum and ascending colon but not the whole colon CITATION Hoy15 \l 1033 (Hoy, 2015). Budesonide MMX is dissolved at a pH of seven or above which means it is uniformly delivered through the entire length of the colon CITATION Lic16 \l 1033 (Lichtenstein, 2016). Lichtenstein (2016) did a study review of two identical designed randomized trials on the drug Budesonide MMX. The studies reviewed included budesonide MMX 9mg and 6mg versus mesalamine 2.4g versus placebo taken daily for eight weeks CITATION Lic16 \l 1033 (Lichtenstein, 2016). The studies Lichtenstein (2016) reviewed concluded that budesonide MMX was well tolerated and remained ulcerative colitis patients in remission long term. Budesonide MMX has the potential to increase adherence as a once a day dose and decrease systematic side effects compared to corticosteroids CITATION Lic16 \l 1033 (Lichtenstein, 2016). There needs to be more research done on the effects budesonide MMX between mild to moderate versus severe ulcerative colitis CITATION Lic16 \l 1033 (Lichtenstein, 2016). There was only two studies reviewed on this medication therefore there needs to be more research done on this medication. Budesonide MMX primarily is absorbed as it passes through the ascending, descending and sigmoid colon (Hoy, 2015). It has a low systematic bioavailability and decreases systemic side effects (Hoy, 2015). Hoy (2015) also reviewed studies on the medication budesonide MMX. Hoy (2015) reviewed articles on this medication and its tolerability and therapeutic efficacy. As a monotherapy, 9mg budesonide MMX was more effective when compared to a placebo for achieving endoscopic remission (Hoy, 2015). There was no drug accumulation observed after seven days and 75% of the mediation was excreted through feces or urine CITATION Hoy15 \l 1033 (Hoy, 2015). Budesonide MMX can be a monotherapy or an add on to 5-ASA to induce remission and the study showed that after eight weeks of combination therapy, there was induced remission CITATION Hoy15 \l 1033 (Hoy, 2015). Side effects of this medication include headache, nausea, and mood and sleep changes but does not include the side effects like a systemic corticosteroid CITATION Lic16 \l 1033 (Lichtenstein, 2016). Systemic corticosteroids are the first choice when choosing a steroid but budesonide MMX should be considered instead because of the low side effects CITATION Hoy15 \l 1033 (Hoy, 2015). There is current research being done on budesonide MMX 6mg as a maintenance medication CITATION Hoy15 \l 1033 (Hoy, 2015). Corticosteroids have been used for decades as a first line choice to induce remission when 5-ASA medications have failed (Cope, 2013). These medications are great to induce remission but should not be used as a maintenance medication because the disease can become infractory (resistant to treatment) as well as produce many local and systemic side effects (Cope, 2013). Steroids are unlikely to induce mucosal healing and physicians need to be aware of short and long term side effects of these medications CITATION Kem13 \l 1033 (Kemp, Dunn, & Schultz, 2013). The corticosteroids used are prednisolone or hydrocortisone on a tapering dose schedule (Cope, 2013). Again, Budesonide MMX once daily has extended release of the drug through the colon and has shown higher remission rates with lower side effects, thus is the popular steroid medication to be used (Cope, 2013). But immunomodulators are widely used when patient becomes steroid dependent CITATION Nie13 \l 1033 (Nielsen, Bjerrum, Herfarth, & Rogler, 2013). Immunomodulators may take months compared to steroids to work but trials have shown mucosal healing CITATION Kem13 \l 1033 (Kemp, Dunn, & Schultz, 2013). Biologic Therapy. Biologic therapy with anti- TNF’s are used to treat moderate to severe ulcerative colitis and is associated with decrease hospitalization and surgeries CITATION Geo15 \l 1033 (George, Gadani, Cross, Jambaulikar, & Ghazi, 2015). Anti-TNF medications include, infliximab, adalmumab, and certolizumab (George et al., 2015). These medications treat chronic inflammation and were originally used for Rheumatoid Arthritis and psoriasis and are now approved for the use of IBD CITATION Mos15 \l 1033 (Mosil, Al-Harbi, Feagan, & Almadi, 2015). Infliximab was approved in 1998 by the FDA for the use to maintain remission and is a popular medication CITATION Kem13 \l 1033 (Kemp, Dunn, & Schultz, 2013). Clinical benefits of infliximab are inducing and maintaining remission (Kemp et al., 2013). Treatment with biologics are restricted by costs and side effects (Kemp et al., 2013). The physician needs to consider timing, commitment, screening and monitoring the patient before choosing a biologic (Kemp et al., 2013). Infliximab has shown to be effective in moderate to severe ulcerative colitis as a rescue medication (Rosen et al., 2015). Rosen et al. (2015) conducted a literature review that focused on those with acute severe ulcerative colitis (ASUC) with anti-TNF therapies. Results concluded that patients with ASUC may exhibit increased rapid clearance of anti-TNF biologics (Rosen et al., 2015). Those with ASUC have higher serum and mucosal TNF burden to quickly absorb and bind anti-TNF medications (Rosen et al., 2015). This could be why there is a rapid clearance of this medication (Rosen et al., 2015). The TNF concentration levels were higher in disease severity which act like a sponge to quickly adsorb anti-TNF antibodies to clear the medication (Rosen et al., 2015). The severe inflammation may increase the activity of phagocytes that “eat” the anti-TNF medication (Rosen et al., 2015). ASUC can have protein losses through the diseased colon which could also explain the low anti-TNF levels (Rosen et al., 2015). This review concluded that weight based dosing may not be effective with ASUC patients due to rapid clearance and an alternate dosing regimen needs to be utilized for therapeutic effects (Rosen et al., 2015). The use of medications to treat ulcerative colitis comes with various side effects that may interfere with the treatment plan. One study touched on the negative effects of anti-TNF’s medication and their association with psoriasiform skin lesions CITATION Geo15 \l 1033 (George, Gadani, Cross, Jambaulikar, & Ghazi, 2015). George et al. (2015) conducted a retrospective chart review for ulcerative colitis and Crohn’s disease patients being treated with anti-TNF medications that developed psoriasiform skin rash. The FDA adverse event reporting systems (AERS) found an increase in psoriasifrom skin lesions with anti-TNF when compared to other therapies such as AZA, 6-MP or methotrexate (George et al., 2015). The risk factors found associated with this medication and skin rashes were female, white, obese and a former or current smoker (George et al., 2015). The lesions were noticed usually at week 58 of treatment, and were located on the trunk, scalp and palmo-plantar (George et al., 2015). Fifty percent of those who developed the lesion stopped the medication only to develop reoccurring lesions (George et al., 2015). The limitation of this particular study was the small sample size and not collecting the TNF concentrations to see if maybe drug toxicity lead to these lesions (George et al., 2015). Psoriasis lesions are not the only potential side effect of ulcerative colitis medications.Treatment for ulcerative colitis with the use of anti- TNF’s comes with multiple serious side effects. These side effects include opportunistic infections, such as tuberculosis, and histoplasmosis pneumoastitis CITATION Mos15 \l 1033 (Mosil, Al-Harbi, Feagan, & Almadi, 2015). Before starting patients on this medication they need to be screened for tuberculosis, checked for neutropenia and see if they have immunizations against influenza or pneumonia (Mosil et al., 2015). Other side effects are demyelinating disease, drug induced lupus and worsening of congestive heart failure (Mosil et al., 2015). The use of AZA comes with a risk of developing lymphoma and in young males increases the risk for hepatosplenic T-cell lymphoma (Mosil et al., 2015). If liver enzymes are elevated on two occasions, AZA and 6-MP need to be discontinued and another medication started CITATION Nie13 \l 1033 (Nielsen, Bjerrum, Herfarth, & Rogler, 2013). Thiopurine medications increase the risk for non-melanoma skin cancer (basal or squamous) and need to avoid sun exposure while on this medication (Mosil et al., 2015). Thiopurine can also lead to bone marrow suppression, hepatoxicity or non-hodgkin’s lymphoma CITATION Kem13 \l 1033 (Kemp, Dunn, & Schultz, 2013). Other research also states that the benefits of thiopurines outweighs the risks (Nielsen et al., 2013). The prolong use of corticosteroids is linked to significant morbidity, early mortality, high development of opportunistic infections, and lymphoma (Mosil et al., 2015). Surgical TreatmentsWhen medication treatments have failed or complications have risen for ulcerative colitis patients, the next option is surgery. The standard of care for ulcerative colitis is a restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) CITATION Fic11 \l 1033 (Fichera, Zoccali, Felice, & Rubin, 2011). These patients requiring surgery present in poor condition, malnourished, anemic and immunosuppressed due to steroid and biologic agents CITATION GuJ14 \l 1033 (Gu, Stocchi, & Remzi, 2014). The type of surgery, either total proctocolectomy or total colectomy (TAC), the approach to surgery, laparoscopic or open, and if surgery will be performed in three separate stages, all depend on the patient’s conditions. Open TAC surgery is done when the patient is in a more severe condition and/or the surgery required is urgent (Gu et al., 2014). Healthier conditioned patients may elect, depending on the surgeon, to have a laparoscopic surgery which has proven to have less complications (Gu et al., 2014). Gu et al. (2014) conducted a retrospective chart review of patients who underwent TAC for ulcerative colitis from 2006 to 2010. Overall, open TAC surgery was done on patients who were older in age and had higher BMI (Gu et al., 2014). Other factors found for the use of open TAC was comorbidities, extensive colitis, urgent surgery and surgeon experience (Gu et al., 2014). Laparoscopic TAC surgery has proven to be more of an efficient surgery compared to an open TAC. Open TAC is considered when certain risk factors are present.The new age of laparoscopic surgery for ulcerative colitis patients is using only a single multi-lumen port for the entire TAC surgery making it a “virtually scar less” surgery CITATION Ove16 \l 1033 (Overstraeten, Wolthuis, & D'Hoore, 2016). In this new age surgery, the port is placed in the anus for easy access to the pelvic floor or at the future stoma site (Overstraeten et al., 2016). In May 2010, the single incision laparoscopic surgery was a preferred choice for surgery CITATION Fic11 \l 1033 (Fichera, Zoccali, Felice, & Rubin, 2011). This approach has multiple advantages over an open TAC. Fichera, et al. (2011), followed nine patients with ulcerative colitis that underwent a single incision laparoscopic TAC from May to October 2010. This single lumen laparoscopic surgery is faster, safer, and has been associated with reduction in morbidity (Fichera et al., 2011). Results included a reduction in the length of the hospital stay (5.1 days compared to 7.2 days), site infections and postoperative pain narcotic use (Fichera et al., 2011). Resumption of diet and bowel activity is increased as well as earlier continuation of activity (Fichera et al., 2011). The most important outcome of this type of surgery is the improvement of cosmetics and improved body image (Fichera et al., 2011). The limitations to this study was a small sample size of twenty patients and cannot be generalized to a larger population. Patients need to be selected carefully based on medical conditions, body habitus and past surgeries (Fichera et al., 2011). The single multi-lumen port laparoscopic surgery does have a learning curve for skilled physicians to learn and be component to perform this procedure (Fichera et al., 2011). Other limitations overall for the single port laparoscopic TAC there needs to be more research done before the single port TAC can be performed on patients with severe ulcerative colitis CITATION GuJ14 \l 1033 (Gu, Stocchi, & Remzi, 2014). Another aspect are those patients whom are having the TAC surgery for removal of dysplasia and developing colorectal carcinoma CITATION Sam15 \l 1033 (Sameshima, et al., 2015). Sameshima et al. (2015) studied 41 ulcerative colitis patients that underwent surgery for associated dysplasia and or carcinoma. Ileal pouch anal-canal anastomosis (IPACA) is the preferred choice for ulcerative colitis patients with dysplasia or carcinoma compared to IPAA surgery CITATION Sam15 \l 1033 (Sameshima, et al., 2015). IPACA was found to be the preferred surgery choice because the whole colon and rectal mucosa was removed to prevent future development of carcinoma CITATION Sam15 \l 1033 (Sameshima, et al., 2015). Surveillance colonoscopy is essential for detecting early dysplasia CITATION Sam15 \l 1033 (Sameshima, et al., 2015). Since 1991, the rate of patient admissions to the hospital for ulcerative colitis complications have increase 170% CITATION Gel14 \l 1033 (Geltzeiler, et al., 2014). Geltzeiler et al. (2014) conducted a retrospective review on data of ulcerative colitis patients nationwide to collect data on initial surgeries of TAC. The number of patients required to have TAC has increased by 44% and subsequent operation for pouch reconstruction has increased by 54% CITATION Gel14 \l 1033 (Geltzeiler, et al., 2014). Infliximab has decreased the rate of colectomies but the long term affect has been unclear CITATION Gel14 \l 1033 (Geltzeiler, et al., 2014). More aggressive management has occurred since the introduction of biologic medications but there is also an increase in TAC surgeries performed suggesting that the use of these medications cannot prevent TAC surgeries in the long term CITATION Gel14 \l 1033 (Geltzeiler, et al., 2014). In the past TAC surgery was only used on acute ill patients but with the increase of TAC surgeries there is a suggestive correlation that more patients are presenting ill. This may mean that these new medication therapies are only meant to be used as a short term therapy or to delay the TAC surgery CITATION Gel14 \l 1033 (Geltzeiler, et al., 2014). Surgeons have said that if the patient has been on infliximab prior to surgery, they delay the pouch construction due to pouch complications with infections due to suppressed immune system CITATION Gel14 \l 1033 (Geltzeiler, et al., 2014). The kock pouch (KP) surgical procedure for ulcerative colitis patients was first developed in the 1960’s but was decreased in the 1980’s due to the development of the ileal anal pouch (IAP) approach (Crawshaw, Williams, & Woodhouse, 2014). The KP approach is still performed when the IAP cannot be done (Crawshaw et al., 2014). The KP is an internal pouch created with the ileum that eliminates the protruding stoma and allows the patient control of bowel “movements” (Crawshaw et al., 2014). A ‘nipple’ is made where a catheter can be inserted to drain the stool when patients’ get a full abdominal sensation (Crawshaw et al., 2014). This way of having a bowel movement has improved the quality of life, sexuality and body image of ulcerative colitis patients (Crawshaw et al., 2014). But, there are complications that accompany this procedure such as seepage, slippage, pouchitis, fistula, stricture and multiple surgeries (Crawshaw et al., 2014). A survey study was performed in the United Kingdom by Crawshaw et al.(2014) that asked patients with a KP their experiences and the responses were overall positive. Those who answered the survey felt that the KP was a better option then the ileostomy (Crawshaw et al., 2014). They had good pouch function/control and a sense of confidence (Crawshaw et al., 2014). The negatives accompanying this procedure is that more than half of the patients had undergone more than one surgery due to complications and that not all patients are suitable for this procedure (Crawshaw et al., 2014). Surgeons and nurses are not familiar enough to perform the surgery or take care of these patients (Crawshaw et al., 2014). Patients need to have good hand eye coordination and hand dexterity with the KP pouch to be able to drain it (Crawshaw et al., 2014). Today, this procedure is rarely performed but from this survey study, ulcerative colitis patients suggest a different opinion regarding the kock pouch (Crawshaw et al., 2014).ConclusionUlcerative colitis is an extremely complex, chronic disease that affects a large population in the United States. The treatments include medications and/ or surgeries. The ultimate goal for medication management is to induce and maintain remission (Gordon et al., 2016). The medication indicated for treatment are, 5-AZA, corticosteroids, immunomodulatory and anti-TNF. The ultimate goal for operations for ulcerative colitis is the removal of all the diseased and disease prone mucosa to achieve a cure CITATION Gel14 \l 1033 (Geltzeiler, et al., 2014). Surgical procedures done for ulcerative colitis include either open or laparoscopic IPAA, IPACA, TAC or kock pouch. Treatment depends on many factors such as patient evaluation, drug tolerance, availability to care, occupation, family support and costs CITATION Fre12 \l 1033 (Freeman, 2012). Chronic relapsing imposes a burden on the healthcare system with alternative medication use, hospital admissions and surgeries CITATION Lic16 \l 1033 (Lichtenstein, 2016). Only one third of patients will achieve sustained remission CITATION Kem13 \l 1033 (Kemp, Dunn, & Schultz, 2013). This creates an urgent unmet need for new therapies in the future (Kemp et al., 2013). The provider, nurse practitioner, needs to tailor each patient to a treatment option through trial and error. References BIBLIOGRAPHY Blonski, W., Bucher, A. M., & Lichtenstein, G. R. (2014). Treatment of Ulcerative Coltis . Curr Opin Gastroenterol, 30(1) , 1-13.Cope, G. (2013). Emerging pharmaceutical therapy for the treatment of ulcerative colitis . Gastrointestinal Nursing, 11(9), 36-41.Crawshaw, A., Williams, J., & Woodhouse, F. (2014). The Kock Pouch Reconsidered: an Alternative Surgical Technique. British Journal of Nursing 23 (17), S26-S29.Dunphy, L. M., Winland-Brown, J. E., Porter, B. O., & Thomas, D. J. (2015). Primary Care 4th ed. Philadelphia: F.A. Davis Company .Fichera, A., & Zoccali, M. (2012). Single-Incision Laparoscopic Total Abdominal Colectomy for Refractory Ulcerative Colitis. Surgical Endoscopy, 26, 862-868.Fichera, A., Zoccali, M., Felice, C., & Rubin, D. T. (2011). Total Abdominal Colectomy for Refractory Ulcerative Colitis. Surgical Treatment in Evolution. J Gastrointest Surg, 15, 1909-1916.Ford, A., Achkar, J., Khan, K. J., Kane, S. V., Talley, N. J., Marshall, J. K., & Moayyedi, P. (2011). Efficacy of 5- Aminosalicylates in Ulcerative Colitis: Systematic Review and Meta-Analysis . The American Journal of Gastroenterology, 601-616.Ford, A., Khan, K. J., Achkar, J., & Moayyedi, P. (2012). Efficacy of Oral vs. Topical, or Combined Oral and Topical 5-Aminosalicylates, in Ulcerative Colitis: Systematic Review and Meta-Analysis. The American Journal of Gastroenterology, 167-176.Freeman, H. (2012). Medical Management of Ulcerative Colitis with a Specific Focus on 5-Aminosalicylates. Clinical Medicine Insights: Gastroenterology, 77-83.Geltzeiler, C. B., Lu, K. C., Diggs, B. S., Deveney, K. E., Keyashian, K., Herzig, D. O., & Tsikitis, V. L. (2014). Initial Surgical Management of Ulcerative Colitis in the Biologic Era . Diseases of the Colon & Rectum, 57 (12), 1358-1363.George, L., Gadani, A., Cross, R. K., Jambaulikar, G., & Ghazi, L. J. (2015). Psoriasiform Skin Lesions are Caused by Anti-TNF Agents Used for the Treatment of Inflammatory Bowel Disease . Digestive Disease of Sciences, 60, 3424-3430.Gordon, G. L., Zakko, S., Murthy, U., Sedghi, S., Pruitt, R., Barrett, A. C., . . . Lichenstein, G. R. (2016). Once-daily Mesalamine Formulation for Maintenance of Remission in Ulcerative Colitis . Clinical Gastroenterol, 50(4), 318-325.Gu, J., Stocchi, L., & Remzi, F. H. (2014). Total Abdominal Colectomy for Severe Ulcerative Colitis: does the Laparosopic approach really have benefit? Surgical Endoscopy, 28, 617-625.Hoy, S. M. (2015). Budesonide MMX: A Review of Its Use in Patients with Mild to Moderate Ulcerative Colitis . Drugs, 879-886.Kemp, R., Dunn, E., & Schultz, M. (2013). Immunomodulators in Inflammatory Bowel Disease: An Emerging Role for Biologic Agents. BioDrugs, 5, 585-590.Lichtenstein, G. R. (2016). Budesonide Multi-matrix for the Treatment of Patients with Ulcerative Colitis. Digestive Disease and Sciences, 358-370.Mosil, M., Al-Harbi, O., Feagan, B. G., & Almadi, M. A. (2015). A Saudi Gastroenterology Association Position Statement on the Use of Tumor Necrosis Factor- alfa Antagonists for the Treatment of Inflammatory Bowel Disease. The Saudi Journal of Gastroenterology, 21(4), 185-197.Nielsen, O., Bjerrum, J. T., Herfarth, H., & Rogler, G. (2013). Recent Advances Using Immunomodulators for Inflammatory Bowel Disease. The Journal of Clinical Pharmacology, 53(6), 575-588.Overstraeten, A., Wolthuis, A. M., & D'Hoore, A. (2016). Transanal completion proctectomy after total colectomy and ileal pouch-anal anastomosis for ulcerative colitis: a modified single stapled technique . The Association of Coloproctology of Great Britain and Ireland, 18, 0141-0144.Rosen, M., Minar, P., & Vinks, A. A. (2015). Review article: applying pharmacokinetics to optimise dosing of anti-TNF biologics in acute severe ulcerative colitis . Alimentary Pharmacology and Therapeutics, 1094-1103.Sameshima, S., Koketsu, S., Takeshita, E., Kubota, Y., Okuyama, T., Saito, K., . . . Oya, M. (2015). Surgical Resections of Ulcerative Colitis associated with Dysplasia or Carcinoma . World Journal of Surgical Oncology , 1-4.What are Crohn's & Colitis? (2016). Retrieved from Crohn's & Colitis Foundation of America: , L., Li, J., Chen, G., Yuan, Y., & Chen, Q. (2014). 5-Aminosalicylates Reduce the Risk of Colorectal Neoplasia in Patients with Ulcerative Colitis: An Updated Meta-Analysis. PLOS, 9(4), 1-10.Appendix AStudiesFocusSubjectsPopulationAgeMethodFindings Blonski, et al(2014). TreatmentsUlcerative colitis, TNF, corticosteroids & 5-ASAUlcerative colitis patientsNo age reported Review of medication treatments Anti-TNF initiated in patients with acute severe refractory corticosteroids in mod/severe UC. Conventional treatment w/ 5-ASA, immunomodulators, corticosteroids. Alt. medication golimumabCrawshaw et al. (2014)Kock pouchN=27 U.K. w/ kock pouch, majority female, outpatient basis45-76 years oldSurveyKP rare procedure in U.K., not the best treatment option for UC patients. Those living with KP have positive thoughts on this procedureFichera et al. (2011)Laparoscopic surgery for total abdominal colectomy in UC patientsN=1010 had surgery & was cased matched to 10 previous lap-assisted (Feb. 03-Jan. 07) & 10 hand assisted (Feb. 06-Ap. 2010)Ulcerative colitis patients underwent surgery TAC, hand assisted or lap. Age not reportedRetrospective reviewed data collection & reviewed statistical analysisNo difference in demographic info., smoking, duration, severity of disease, single incision. pts were more likely to have received immunosuppressive therapy 30 days prior to surgery. Single lap. shorter duration surgery. Faster diet resumption then other groups Ford et al. (2012)Efficacy of oral vs. topical 5-ASAN=124= topical/oral4= combined 3= intermittent topical/oral2= combined oral 5-ASAActive UCNo age reportedSystematic review & meta-analysisCombined 5-ASA superior to oral to induce remission of mild/moderate active UC. Intermittent topical 5-ASA superior to just oral Ford et al. (2011)Efficacy of 5-ASAN=375 ASA active UC=195 ASA quiescent lap approach=18Active UC remissionNo age reportedSystematic review & meta-analysis 5-ASA highly effective reduce remission & prevent relapse US. Dose >2g/day effective. Doses 2.5g/day > do not appear to lead higher remission ratesFreeman (2012)UC management 5-ASA5-ASA articles specifically SulfasalazineUC patientsNo age reportedReview of articles5-ASA products used to induce remission mild/moderate UC distal/extensive. Can be used along with steroids. Dose 1-5gm.Geltzeiler et al. (2014)Surgical managementN=1,547,852 pts w/ UC admitted hospital in the U.S. btw 1991-2011UC patients diagnosed with appropriate ICD-9 codeAge not reportedRetrospective review of data using Nationwide Inpatient Sample DatabaseUC related admission rose by 170% the number of patients TAC rose 44%. Pouch reconstruction rose by 16% as subsequent surgery since 2008. TAC has surpassed proctocolectomy StatusFocusSubjectsPopulationAgeMethodFindingsGeorge et al. (2015)Anti-TNF agents used for IBD cause psoriasisform skin lesionsN= 521 w/IBD w/ TNF treatment16=Crohn’s2=UC72= controlCrohn’s and UC pts w/ and w/o psoriasisfrom lesions. White, femaleNo age reportedCase control study calculated statistical analysisLesions developed at mean of 58 weeks after starting TNF therapies. Majority former/current smokers. Lesions located trunk, scalp & palmo-plantar. 3.5% lesions developed in IBD pts Gordon et al. (2016)Mesalamine formulation remissionN= 257Mesalamine granule use n=164Placebo n=93UC in remission96% white52% femaleMild/ moderateNo age reportedPhase 3 randomized double blind placebo controlled trialGreater number of patients received mesalamine granules were in remission at 6months. 79.9% vs. 66.7% placebo. 1.5g daily was tolerated w/ minimal side effects. Patients were 97% compliantGu et al. (2014)Total abdominal colectomy (TAC) severe UC. LaparoscopicN=412N=197 underwent lap. ApproachPatients undergoing TAC for UC 2006-2010Lap= 33 years oldOpen= 42 years oldChart review statistical analysis 197 patients for Lap. TAC were younger, had increase Hg & albumin. Lap. Surgery longer operation times, decreased blood loss, shorter postop. Stay. Increased portion open TAC performed urgently. Complication increased after open TACKemp at el. (2013)Immunomodulators in IBDArticles containing TNFCrohn’s & UC patients No age reportedReview of articlesTNF targeting drugs have proved major milestone. Restricted by cost & side effects. To start this med- timing, commitment, screening, monitoring. Still 2nd line therapy choiceLichtenstein (2015)Budesonide multi matrix treatmentArticles containing UC & the use of budesonide MMXUC patientsNo age reportedArticle reviewBudesonide MMX delivers drug through whole colon. Well tolerated & induce remission mild/mod UC. Long term safety was comparable to placebo once a day dosing, increased adherence Nielson et al. (2012)Immunomodulators for IBDArticles containing AZA, 6-MP, MTX. Pharmacokinetics, pharmacogenetics, therapeutic, blood testing & adverse eventsUC &/or Crohn’s patientsAge not reportedComprehensive reviewImmunomodulators used widely in treatment of steroid-dependent or steroid refractory IBD as mono or combination therapy w/ biologicsOverstraeten et al. (2016)Procolectomy post total colectomy, modified single staple techniqueUC patients who went for future transanal completion proctecolectomy. Post TAC ileal pouch- anal anastomosis for UCUC patients requiring surgery. Multiport lap =6 single port =5Age not reportedStep by step approach to ta-IPAA surgery in UCDescription of ta-IPAA single port lab. In all 11 pts, stoma site was used for single port. Completion of proctecolectomy was done transanal. Single stapled anastomosis was performed in all pts.Rosen et al. (2015)PharmacokineticsArticles from databases containing key words ‘UC’, ‘acute severe UC’, ‘anti-TNF & pharmacokinetics’Acute severe UC patients using TNF therapyKids & adultsComprehensive review TNF for suboptimal outcomes. Half of kids/adults went for colectomy. Pts w/ acute severe UC exhibit rapid clearance. TNF biologics due to pharmacokinetics influenced by disease severityStudiesFocusSubjectsPopulationAgeMethodFindingsSameshima et al. (2015)Surgical resectionN=41 UC patients n=12 associated dysplasiaUC patients w/ dysplasia or carcinomaMale=10Female=2Mean age 58Systemic review10 cases primary operation, 2 cases 2nd line operations. 7/10- anus & anal sphincter preserved & permanent colostomy avoided. 5 IPACA had HALS performed instead w/ difficulties w/ stapling anastomosis. 12 cases confirmed dysplasia or carcinoma Zhao et al. (2014)5-ASA reduce risk of colorectal neoplasia17 articles 1994-2012Use 5-ASA in patients w/ UC or IBDAge not reportedMeta- analysis5-ASA associated w/ reduced risk of colorectal neoplasia in U.S. especially in those using higher average dose ................
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