Section 5 Dietary Therapy

#### **Chapter 8**

## Dietary Fermented Rice Bran Is an Effective Modulator of Ulcerative Colitis in Experimental Animal

*Afroza Sultana, Abul Fazal Mohammad Nazmus Sadat and Md. Alauddin*

#### **Abstract**

Ulcerative colitis (UC) is an inflammatory disorder with colon and rectum, characterized by recurring bloody diarrhea due to microbial dysfunction and some autoimmune response. Scientists have linked microbial disruption in the gut to several chronic conditions such as UC and other types of inflammatory bowel disease (IBD). Surprisingly, our gastrointestinal tract contains more than 100 trillion microbial cells. Some microbes in the gut microbiome are friendly bacteria that can help to treat UC by influencing metabolism, nutrition, immune function, and more in the gut. The conventional medical treatment of UC relies on the use of amino-salicylates, corticosteroids, immunosuppressive drugs, glucocorticoids, and antibiotics. Multiple new mechanisms in the treatment of UC are being developed and many are showing promising results in ulcerative colitis. Still need scientific evidence to support the role of gut microbiota in the etiology of UC. The dietary fermented rice bran (DFRB) may include the active potential for the treatment of ulcerative colitis. The DFRB may attenuate intestinal inflammation by regulating gut permeability for cellular infiltration and maintenance of luminal safety with favorable efficacy in UC. In this chapter, we discussed and summarized the insight mechanism of DFRB's modulatory activities for the management or treatment of ulcerative colitis.

**Keywords:** ulcerative colitis, fermented rice bran, gut microbiome, intestinal homeostasis, and tight junction barrier integrity

#### **1. Introduction**

Chronic inflammatory disease, ulcerative colitis (UC) is recognized by the luminal abnormalities by the flourishing of cytokines at the large intestine that can cause irritable mucosal lining cells and disruption of tight junction protein [1]. UC is one form of inflammatory bowel disease (IBD) and the severity was first coined in the 18th century [2]. Another form of this (IBD) disease is known as Crohn disease (CD). Worldwide, both diseases are commonly termed IBD and the frequency of this disease is observed commonly not only in the first world countries but also

increasing this scenario in Asian countries due to their dietary habits. Surprisingly, the severity of this disease was found more common in Caucasians than other racial and colors people based on their lifestyle and food habits and as well as remarkably increased in Jewish [3]. The disease severity was found to be age dependent and the onset of the disease is 30–40 years old among the men and women equally [4]. The complexity of this disease makes a debilitating disorder by the discontinuous lacerations in the gut mucosal cell [5]. But the mechanism of inflammation in UC is typically confined in the mucosal cell lining that is the main cause of damage of the bowel wall and ultimately loss of mucosal tight barrier in the intestinal tract [6]. This mechanism has occurred recurrently in the mucosal cell lining leading to bloody diarrhea, which is the most common symptom of UC, although diagnosis is made from a combination of symptoms, endoscopy and histology [6]. The common symptom of UC is not only diarrhea with the blood but also some other symptoms sometimes less found with abdominal pain, body temperature, and weight loss [7]. The different types of UC can be recognized by the extent of the disease such as proctitis, this type of UC is limited to the end of the colon. Proctosigmoiditis is found in the rectum and sigmoid colon. The left-sided and extensive colitis is confined to and beyond splenic flexure [6, 8, 9]. The disease severity of UC is categorized as mild, moderate, severe, and fulminant with stool output category. If the stool output frequency is four per day with or without bloody is called mild, and more than four bloody stools per day is called moderate, more than six bloody stools per day is called severe and more than 10 bloody bowel movements with abdominal distention is called serious or fulminant colitis. UC disrupts not only the intestinal integrity but also predominantly affects the immunologic skin, joining part of the body, vision of eyes, and the most important organ liver [1, 6, 8, 9]. Similarly, different arthritis such as peripheral or axial and narrowing bile duct disease are also accompanying UC [1, 9]. The consequence of pathologic outcome for UC depends on dietary habits and environmental factors that can affect the host immunologic response, and ultimately change the microbiota symbiotic action in hereditarily vulnerable characters [10]. Dietary habits with lower fiber-based processed food and fewer intake of plant-based meals in lifestyle could be attributed to the augmented incidence of UC in the Asian population. A recent review article showed that the risk of UC is inversely associated with the herbal intake, they also found that the risk of UC is directly associated with total fat intake including Omega-6 fatty acids and meat [11].

In that connection food supplements are the important modulators of UC. The dietary habit with high fiber, multivitamins, free amino acids, bioactive compounds for antioxidants may be considered as the effective potential to encourage digestive health [12].

#### **2. Etiology of ulcerative colitis**

Even while its specific cause is still unknown, various contributing variables have been implicated such as an immunological response that is out of control, altered gut microbiota, genetic susceptibility, and environmental factors. The etiology of UC is primarily initiated by the invasion of inflammatory molecules to the intestinal tract changing the microbiota and ultimately loss of intestinal integrity causing bloody diarrhea [13]. The actual pathophysiologic pathway of UC remains elusive, but the number of studies postulated that overstimulation of immunologic function and insufficient

#### *Dietary Fermented Rice Bran Is an Effective Modulator of Ulcerative Colitis in Experimental… DOI: http://dx.doi.org/10.5772/intechopen.102848*

control of mucosal barrier integrity leads to cell infiltration and inflammation in the intestinal tract [3]. The gastrointestinal tract is the main part of the body for digestion, absorption metabolism, and control of immunity for normal health. Disruption of this pathway may affect the deregulation of microbiota and mucosal immunological function is the main cause of propagation of UC [14, 15]. Deregulation of normal microbiota may change the pro-inflammatory molecules such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6, which are responsible for colonic tissue damage and gut bleeding leading to ulceration of the colon. The intestinal tract contains a lot of microorganisms called microbiota, primarily bacteria; some other organisms including viruses, archaea, and fungi are responsible for inhibiting the gastrointestinal tract [16]. For example, the proteobacteria phylum, among other bacterial species, have been demonstrated as microbial initials in inflammatory bowel disease (IBD) for gut microbiota in IBD patients [17]. The non-eligible function of proteobacteria has been found for the development of IBD. The proteobacteria such as *E. coli*, was found to be disproportionately proliferated leading to the development of IBD [18]. This bacterial proliferation may influence the infiltration of severe and continuing provocative cells in the intestinal lumen. This provocative infiltration predominantly increases the mucosal immunoglobulin G production, subsequently chemoattractant complement activation leading to aggregation, and ultimately enhancement of macrophages and T cells. This cascade of immunological activity is connected with the discharge of inflammatory cytokines, kinins, leukotrienes, platelet-activating factor (PAF), and reactive oxygen metabolites in the gastrointestinal tract for initiation of IBD. The mechanism of these mediators that amplify the immune and inflammatory response not only the main cause but also have deviating effects on epithelial cell function which may increase the permeability, this is the cause of ischemia The mediators may influence on repair mechanisms in the colon, thus increasing the biosynthesis of collagen leading to the fibrosis process in the intestine, one of the causes of the intestinal bleeding. In addition, the acute phase striking forces such as IL-1, IL-6, and TNF-α will activate a chronic response in the intestinal lumen and ultimately. The resulting storm can cause fever in the body with an increased level of serum acute-phase proteins [19–22]. The detailed mechanism of intestinal increased permeability due to the cytokines storm is not completely stated, but an association with increased permeability due to the bacterial translocation into the lamina propria that could exacerbate the loss of tight junction protein and loss of barrier function [20].

#### **3. Summary of possible mechanisms of UC treatment pathway**

As the detailed mechanism of UC disease is unclear, so that there are no known single preventive or curative interventions or safe colectomy therapy was found in most of the IBD patients for lifelong [21]. Up to date most of the therapeutic treatments are able to inhibit the beginning of immunological and inflammatory effectors, loss of integrity protein, regulation of inflammatory cytokines, and loss of intestinal barrier mechanisms. These therapeutic strategies may lead to an improvement in the patient's symptoms and decrease inflammatory activity [1]. Several functional compounds and their metabolites may inhibit the UC progression. **Table 1** and **Figure 1** describe the possible mechanisms of UC treatment pathways that are commonly observed in the dextran sulfate sodium (DSS)-induced UC animal model**.**


*Dietary Fermented Rice Bran Is an Effective Modulator of Ulcerative Colitis in Experimental… DOI: http://dx.doi.org/10.5772/intechopen.102848*


#### **Table 1.**

*Prospective pathways and modulators for minimizing UC (revised from the experiment on dextran sulfate sodium (DSS) induced UC animal).*

#### **4. Dietary fermented rice bran (DFRB) as an alternative modulator for ulcerative colitis treatment**

The by-product of the rice grain is called rice bran (RB) a valuable and low costing source of biologically active components that is currently available in most regions of the world. It has been possible to improve the quality or make RB edible for humans by using RB procedures such as bacterial fermentation. In contrast to typical raw bran, treated RB or nutritionally enriched dietary fermented rice bran (DFRB) include more basic nutrients such as proximate composition and bioactive compounds [49]. Rice bran is one of the most plentiful agricultural products in Asian countries and is a superb source of nutritional fiber, protein, and fat [50]. RB has been recently claimed for its nutraceutical properties; specific components of the lipid fraction of RB such as tocotrienols, a group of compounds with vitamin E [51]. The difficulty of its use is because of its excessive fiber content material, low protein, and antinutritional elements along with phytic acid [52]. Most of the dietary fiber content in RB belongs to the class of insoluble dietary fiber which may be beneficial for increasing fecal bulk and laxation [53].

*Ulcerative Colitis - Etiology, Diagnosis, Diet, Special Populations, and the Role of Interventional…*

**Figure 1.** *Anti ulcerative effects observed in experimental animal.*

#### **4.1 Nutritionally enriched dietary fermented rice bran**

Recent studies have suggested that fermentation can improve their biological activities. Fermenting is the process of naturally gathering wild cultures and yeasts from the air and combining them with an organic substance. During the fermentation process, sugars and starches contained in the feed ingredients are broken down into lactic acid bacteria (LAB). The lactic acid formed by the action of LAB from substrate sugars through pyruvate (a glycolysis end product) plays an important role in food fermentation. Fermentation technology produces not only lactic acid, but also other end products such as ethanol, acetic acid, and formic acid depending on bacterial species and conditions [54]. The lactic acid bacteria produced during fermentation promote the growth of beneficial microbes called probiotics. These improve the digestive system health and boost the immune system. Feed fermentation is a complex process that depends on the nutritional requirements and digestive physiology of animals, the nutritive value of feedstuffs, fermentation characteristics of the microorganisms added to the starter culture, and actual situations on individual farms [55]. Systematic use of bacteria may improve desired food ingredients in the diet.

Previous studies reported that *Bacillus amyloliquefaciens* may successfully produce various enzymes such as αamylase, α-acetolactate, decarboxylase, β-endoglucanase, hemicellulase, phytase, maltogenic amylase, and xylanase, which possess the

#### *Dietary Fermented Rice Bran Is an Effective Modulator of Ulcerative Colitis in Experimental… DOI: http://dx.doi.org/10.5772/intechopen.102848*

potential to degrade fiber [56]. Some lactic acid bacterial strains can produce Exopolysaccharides (EPS), which exert health-promoting effects as a function of prebiotics. The EPS may be responsible for the immunomodulator action [53]. Due to the significant increment of protein content in the fermented rice bran, the quality of this produced compound is the target of interest. Dietary fermented rice bran (DFRB) has been interested in particular for the treatment of unfavorable duodenal inflammation. DFRB supplementation would be able to alter intestinal inflammation caused by DSS-induced colitis. The evidence of DFRB was found to raise the amounts of striking modulators such as short-chain fatty acids and other microbial metabolites in the gastrointestinal tract. Tryptamine is one of them which comes from tryptophan metabolism in the intestine by beneficial microorganisms. The striking modulator metabolites may regulate the intestinal loss of tight junction barrier and ultimately intestinal microbiota homeostasis. The preventive action of DFRB may be partially due to the availability of bioactive compounds during fermentation of rice bran, such as polysaccharides, carbohydrate conjugated proteins, γ-oryzanol, plant sterols, and antioxidant vitamin E. DFRB is very important for the regulation of IBD patients because of fermentation technique make its bioactive compounds more accessible and easier to metabolize. Several studies have pointed out that fermentation technologies enhance the amount of the total phenolic content, short-chain fatty acids, amino acids, and other metabolites that can ameliorate intestinal inflammation. Consequently, it is prospective that DFRB can be used not only as a protective measure but also as a beneficial mediator against an ongoing intestinal inflammation like UC [49, 57–60].

#### **4.2 DFRB as ulcerative colitis modulator**

One of the enriched ingredients of DFRB is tryptamine, 5-hydroxytryptamine comes out as bacterial metabolites. These metabolites are considered an effective modulators for the candidate against UC [7, 14]. Tryptophan, one of the boosted constituents in DFRB, is recognized as an effective modulator for UC [7, 14]. Tryptamine and 5-hydroxytryptamine derived from tryptophan, can act as a ligand for the receptor of the aryl hydrocarbon, which modulates immunologic cytokines IL-22 gene production, controls autoimmune, and facilitates fast recovery from colitis in the large intestine. Some insoluble DFRB may also stimulate the microbial proliferation and production of short-chain fatty acids (SCFAs), particularly, acetic acid (AA), propionic acid (PA), butyric acid (BA), and lactic acid (LA), which are strappingly linked with the colonic health in DSS induced UC [15, 49].

A single modulator for the treatment of IBD seems difficult to pinpoint due to the intricate interplay of various variables. For individuals with IBD, the use of biologically effective significant functional compounds such as anti-tumor necrosis factor (TNF) drugs have lowered early surgery. Nevertheless, there are still many difficulties with current treatment intervention and new therapies are highly required. In various experimental murine colitis models, many single substances or combinations made from natural commodities based on traditional usage knowledge have shown promising anti-inflammatory qualities with minimal negative effects and have the potential to be next-generation therapeutics. Even now, clinical studies are being conducted on several plants' small components, including berberine, curcumin, epigallocatechin-3-gallate (EGCG), and triptolide. There is a new IBD treatment in the works, a recovered anti-mycobacterium drug (Oral capsule RHB-104, here, RHB-104 = Red hill biopharma, an investigational drug), now in phase III clinical trials. The current

therapy challenges associated with numerous side effects might be greatly improved by using a suitable and non-invasive IBD medication that targets specific receptors in the colon. Ethnopharmacology-guided drug discovery, with a particular emphasis on tiny molecules and peptides of medicinal plants, has the potential to generate safe and new therapies for IBD. Clinical and histological damage to the colon is both reduced by a cardiotrophin (CT)-1 injection before DSS induction. This effect seems to be done by inhibiting inflammation and apoptosis directly and activating the Stat-3 and nuclear factor kappa B (NF-kB) signaling pathways. Stat-3 and NF-kB CT-1 might potentially be expected to be a feasible, innovative method to prevent UC relapse. A fermented diet was included in the regular diet as a supplement. When given a Fermented diet (FD) with DSS for 7 days, mice did not lose weight or suffer from atrophy of the intestinal length. IL-6 and TNF-\_ levels in the mice did not rise after FD treatment, indicating that inflammation was kept under control. People who ate an FPE-enriched diet for 3 months had an increased clostridiales order in their feces, which generates short-chain fatty acids to reduce inflammation. FPE supplementation has been shown to increase the proliferation of Clostridiales in the gut, as well as to reduce inflammation in colitis [61–63].

Another research found that the relative abundance of bacteroidetes species was adversely associated with UC activity and might serve as important microbiological biomarkers to monitor UC disease activity and exacerbation. A reliable and noninvasive method for monitoring UC and establishing personalized therapy might be made possible by identifying components of the microbiome that are associated with disease activity. In mice with inflamed intestines, FRB supplementation helped to heal the damage caused by DSS. DAI scores and the generation of intestinal proinflammatory cytokines were reduced by FRB administration. The anti-inflammatory cytokine Il-10, the tight junction component Clad4, and antimicrobial proteins were all considerably increased by FRB supplementation in the gut. This capacity to inhibit both canonical and non-canonical pathways of Tgf-b profibrogenic activity was also able to reduce the development of fibrosis in mice intestines after inflammation. Using FRB supplements to reduce inflammation is not the only way to repair the intestines in people with chronic colitis, according to the findings of this study. It has been postulated that FRB acts as a prebiotic in the gut, but even if intestinal dysbiosis has developed as a result of inflammation, it may still treat colitis. As a result, the role of FRB supplementation on gut microbiota populations and composition has to be studied further [63–65].

In **Figure 2,** three different conditions of intestinal luminal microbial flora. The movement of luminal microbiota and smoothie mucosal protection has been seen in stage 1, generally is regulated by pro-inflammatory cytokines such as IL-10,IL-1β, IL-4,IL-6,TNF-α, and membrane tight junction protein occludin, ZO-1 and E-cadherin etc. indicate normal expression of cell. In stage 2, the changed luminal microbial diversity (dysbiosis), impaired epithelial, and mucus layer barrier via disruption of tight junctions expressed the intestinal inflammation mediated by Dextran sodium sulfate (DSS). Usually, DSS induced inflammation prompts to disruption of the mucosal layer, with an increased loss of crypts, inflammatory cell infiltration, increased MPO activity, and pro-inflammatory cytokine transcript (Tnf- α, Il-1 β, Il-6, and Il-17) associated with excessive intestinal epithelial permeability via the tight junction of epithelial and by increasing luminal antigen uptaking. That's how Toll-like receptors recognize non-pathogenic bacteria (commensal microbiota) and activate antigen-presenting cell (e.g. TLRs) APC activated T-cells become Th-2 effector cells (which produce

*Dietary Fermented Rice Bran Is an Effective Modulator of Ulcerative Colitis in Experimental… DOI: http://dx.doi.org/10.5772/intechopen.102848*

#### **Figure 2.**

*A simple fictional image of enterocytes associated with normal behavior, inflammatory condition and after treatment with DFRB (review from [62, 67]).*

pro-inflammatory cytokines like TNF-, IL-5, IL-6, and IL-13). TNF and IL-1 activate the NF-B pathway, promoting pro-inflammatory and cell survival genes.

The mucin generation and epithelium integrity appeared in the 3rd stage of this fictional image of intestinal lumen after treating with DFRB and it has been proved by Islam (2017) that, this incidence is facilitated by increased SCFA levels in the colon via inducing colonic regulatory T cells and reducing UC. Also, apoptosis can be induced in mutated epithelial cells through innate immune cell-driven inflammation. To maintain colonic homeostasis and intestinal barrier integrity, these activities are essential. Thus, the integrity of the intestinal barrier helps not only to maintain a healthy relationship between the intestinal microbes and the host but in addition to being a physical barrier, it also serves as a barrier to the entry of invading microorganisms pathogenic microorganisms or their toxins can be detected by an organism's immune system. Tight junctions (TJs) are made up of occludin and a variety of other proteins (OCLN) and claudin (CLDN), which are primarily responsible for determining the integrity of the intestinal barrier. TJs can be found here. At the ends of the epithelial cell's lateral membrane, the loss of TJ barrier integrity is linked to the onset and progression of UC.

The study has shown that transcription factor named by aryl hydrocarbon receptor (Ahr) regulates the expression of IL-22 genes, controls autoimmunity processes, and promotes rapid recovery from colitis by binding to tryptophan-metabolites in the microbiota. DFRB might boost up the microbial power generation of short-chain fatty acids (SCFAs), such as AA, PA, BA, LA, which are intimately connected to colonic health of us, might even be a result of DFRB [61, 66].

#### **5. Future perspective**

A number of fermentation studies on rice bran indicated that the process is capable of producing short-chain fatty acids such as acetic acid, propionic acid, butyric acid, lactic acid, enzymes such as protease amylase, phenolic compound, and antioxidant compound like vitamin E as well as secondary metabolites such as griseofulvin, etc. for treatment of UC [67–74]. Previous studies also indicated that it is possible to change the lipid and phospholipid composition and phenolic acid content and antioxidant activities of rice bran would be the effect modulators for the treatment of UC [75, 76]. In the future, the possibility of DFRB would be the natural source of modulators for the potential regulators of the disease burden. The single-component of DFRB such as short-chain fatty (like Propionate), omega-3 fatty acid (like eicosapentaenoic and docosahexaenoic acid), fibers (both soluble and insoluble), polyphenols (oleanolic acid and salvianolic acids), and even vitamins (C, D, E) may be responsible for specific modulators in the maintenance of gastrointestinal tract health. The detailed experimental data is still needed worldwide. These vibrant modulators could be produced by using suitable variants of bacteria and fungi for fermentation as well as by using recombinant technology to modify the bacteria and fungi for a specific purpose. However, variations in the conformation of duodenal microorganisms are generally responsible for the establishment of gut health in patients with UC. Furthermore, DFRB influences not only the attendance of gastric microbiota but also modulates their metabolites. The interchange of microbes and metabolites by the DFRB would be a good modulator to alter the intestinal defense mechanism against mucosal inflammation for the treatment of UC [23]. The DFRB also modulates impaired DNA integrity that occurs during oxidation after the intestinal inflammation [24]. Hence, the DFRB would be a good candidate for therapeutic treatment of UC rather than a preventive measure, but this scenario still requires many animal experiments. This is a significant peculiarity of DFRB to make a potential modulator, especially in the case of IBD. Whereas the treatments of IBD are generally aimed to prevent a flare-up of enduring inflammation and to hinder its development into an irreversible state such as stricture and altered colonic motility and permeability [66].

#### **6. Conclusions**

The availability of bioactive components in DFRB, such as dietary fiber, vitamins, free amino acids, and antioxidants, ensures the potential of DFRB to improve the health of the gastrointestinal tract (gastrointestinal health). By utilizing fermentation technology, it is possible to incorporate many more nutrients into rice bran, particularly potential UC modulators, than are currently available. The nutritional content of rice bran is typically determined by the fermented organism, the length of time the bran has been fermented, and the source or types of rice bran used. A high level of concentration is required to isolate the specific bacteria, fungi, or yeast that is capable of producing the desired fatty acids, fibers, vitamins, amino acids, anti-inflammatory, antioxidants, and other compounds in fermented rice bran. Using recombinant technology, it may be possible to produce the desired microorganisms for use in the fermentation process, which would then be used to introduce desired nutrition into the DFRB. This will also be beneficial in the treatment of other metabolic conditions in addition to UC colitis.

*Dietary Fermented Rice Bran Is an Effective Modulator of Ulcerative Colitis in Experimental… DOI: http://dx.doi.org/10.5772/intechopen.102848*

#### **Acknowledgements**

I am particularly grateful to Jashore University of Science and Technology for the logistic support of this cha–pter.

#### **Authors contribution**

Md. Alauddin conceived the study design and manuscript preparation. AFM Nazmus Sadat carried out suggestions and data analysis. All the authors contributed to analysis and Afroza sultana contributed to manuscript writing. Md. Alauddin approved the final version of the manuscript.

#### **Conflict of interest**

The authors declare no conflict of interest.

#### **Appendices and nomenclature**


*Ulcerative Colitis - Etiology, Diagnosis, Diet, Special Populations, and the Role of Interventional…*

#### **Author details**

Afroza Sultana1 , Abul Fazal Mohammad Nazmus Sadat2 and Md. Alauddin1 \*

1 Department of Nutrition and Food Technology, Jashore University of Science and Technology, Jashore, Bangladesh

2 Institute of Environmental Science, Rajshahi University, Rajshahi, Bangladesh

\*Address all correspondence to: mdalauddin1181@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Dietary Fermented Rice Bran Is an Effective Modulator of Ulcerative Colitis in Experimental… DOI: http://dx.doi.org/10.5772/intechopen.102848*

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Section 6

## Interventional IBD in Ulcerative Colitis

### **Chapter 9**

## Role of Interventional IBD in Management of Ulcerative Colitis(UC)-Associated Neoplasia and Post-Operative Pouch Complications in UC: A Systematic Review

*Partha Pal, Rupa Banerjee, Mohan Ramchandani, Zaheer Nabi, Duvvuru Nageshwar Reddy and Manu Tandan*

#### **Abstract**

Interventional inflammatory bowel disease (IIBD) is going to play a major role in complex IBD including ulcerative-colitis associated neoplasia (UCAN) and postoperative complications after ileal pouch-anal anastomosis (IPAA) in ulcerative colitis (UC). We performed a literature search in PubMed using keywords such as "UCAN" and "endoscopic management of pouch complications," After screening 1221 citations, finally, 91 relevant citations were identified for the systematic review. Endoscopic recognition of dysplasia should be done by high-definition white light endoscopy (HD-WLE) or dye-based/virtual chromoendoscopy (CE) especially in known dysplasia or primary sclerosing cholangitis (PSC). Endoscopically visible lesions without deep submucosal invasion can be resected endoscopically with endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), or using full-thickness resection device (FTRD). Image-enhanced endoscopy (IEE) and IIBD have an emerging role in screening, diagnosis, and management of colitis-associated neoplasia in UC and can avoid colectomy. IIBD can manage a significant proportion of post-IPAA complications. Pouch strictures can be treated with endoscopic balloon dilation (EBD) or stricturotomy, whereas acute and chronic anastomotic leak or sinuses can be managed with through the scope (TTS)/over the scope clips (OTSC) and endoscopic fistulotomy/sinusotomy.

**Keywords:** ulcerative colitis-associated neoplasia, Ileal pouch-anal anastomosis, interventional inflammatory bowel disease, ulcerative colitis, pouch complications

#### **1. Introduction**

With growing multidisciplinary care model of inflammatory bowel disease (IBD), IIBD is going to play a major role in management of complex IBD. Apart from its major role in management of Crohn's disease-related strictures and fistulas, IIBD has an important role to play in management of colitis-associated neoplasia in ulcerative colitis (UC) and postoperative pouch complications [1, 2]. Ulcerative-colitis associated neoplasia (UCAN) can range from indefinite dysplasia (IND), low-grade dysplasia (LGD), high-grade dysplasia (HGD), invisible dysplasia, and colorectal cancer (CRC). Apart from conventional dysplastic lesions, non-conventional dysplasia (e.g., serrated epithelial change: SEC) can occur in one third. Non-conventional dysplasia increases risk of advanced colorectal neoplasia (aCRN) according to recent meta-analysis and may warrant frequent surveillance [3].

Endoscopic screening should begin at 8−10 years from symptom onset for UCAN in the absence of PSC with subsequent surveillance based on risk stratification. HD-WLE, narrow band imaging (NBI), and CE have similar efficacy in detecting UCAN [4]. The incremental benefit of newer modalities of IEE such as Fuji Intelligent Color Enhancement (FICE), I-SCAN, linked color imaging (LCI), and autofluorescence imaging (AFI) for diagnosis of UCAN compared to conventional screening needs further evaluation. Endocytoscopy and probe-based confocal laser endomicroscopy (pCLE) can be helpful in "in vivo" diagnosis of UCAN [5]. Visible, uni-focal, polypoidal dysplasia of any grade can be resected en bloc using EMR or ESD [6]. For invisible dysplasia, management is dependent on patient-related (e.g., PSC) and histologic factors and includes colectomy. Concurrent inlet strictures in pre-pouch ileitis and anastomotic strictures can be treated with endoscopic balloon dilation or stricturotomy. Stricturing/fistulizing complications of Crohn's disease of the pouch can also be treated endoscopically. Endoscopic sinusotomy and fistulotomy are helpful in treating pouch sinus and fistulas respectively. Endoscopic placement of clips is useful in controlling leaks from pouch. Endoscopic resection can be done for large symptomatic inflammatory polyps in the pouch or polyps in the rectal cuff [2, 7]. We aimed to systematically review all the relevant literature pertaining to endoscopic management of UCAN and pouch complications post IPAA.

#### **2. Search strategy**

For the purpose of the review, we searched the PubMed using keywords "ulcerative-colitis associated neoplasia (UCAN)" and "endoscopic management of pouch complications" We found 965 citations. We also screened relevant articles with specific searches and selected cross references. Finally, after screening, total of 1238 citations, 91 were identified for the systematic review (**Figure 1**).

#### **3. Detection of UCAN**

Among various modalities for detection of dysplasia in IBD (**Table 1**), highdefinition white light endoscopy (HD-WLE), narrow-band imaging (NBI), and chromoendoscopy (CE) were similar in efficacy in detecting UCAN with minor differences among them according to network meta-analysis [4]. Standard definition *Role of Interventional IBD in Management of Ulcerative Colitis(UC)-Associated Neoplasia… DOI: http://dx.doi.org/10.5772/intechopen.106599*

**Figure 1.**

*Consort diagram of systematic review on ulcerative colitis associated neoplasia and post ileal pouch complications.*

white light endoscopy (SD- WLE) was shown to be inferior to all these modalities [4]. Shorter withdrawal time and easy applicability are the advantages of NBI compared to CE whereas dysplasia detection rates are similar [8]. Magnifying endoscopy (ME) has incremental benefits over CE for detecting tumor margins to guide endoscopic resection (ER). ME guided ER has R0 resection rate of 95% (compared to 91% with distinct borders with only CE) [9].

The Japanese NBI expert team (JNET) classification and pit pattern on magnifying virtual/chromoendoscopy can predict histological diagnosis and invasion depth accurately as shown in a retrospective study of UCAN who underwent endoscopic resection or colectomy. JNET 2A, 2B, and 3 lesions imply low grade dysplasia (LGD), LGD/ high grade dysplasia (HGD), and submucosal invasive carcinoma (SMIC). Pit pattern III/IV, VI low irregularity, VI high irregularity/VN can predict LGD, LGD/HGD, SMIC respectively [10]. Among image-enhanced endoscopy, (IEE), Fuji Intelligent Color Enhancement (FICE) can help predict histology of raised lesions in IBD apart from NBI [11]. I-SCAN is another modality of IEE which has a similar diagnostic yield with a shorter examination time than conventional CE [12]. Linked color imaging (LCI) with indigo carmine dye spraying can help facilitate UCAN diagnosis [13]. Endocytoscopy may help in "in vivo" diagnosis of intra-mucosal carcinoma (IMC) by observing enlarged nuclei after methylene blue staining [14]. Endocytoscopy irregularly-formed nuclei with pit (EC-IN-PIT) guided diagnosis of UCAN were shown to have better specificity and diagnostic accuracy than pit pattern alone in a pilot study [15]. Probe-based confocal laser endomicroscopy (pCLE, Cellvizio, Mauna Kea Technologies, Paris, France) can differentiate UCAN (carcinoma or dysplasia) with accuracy, sensitivity, and specificity of 92%, 100%, and 83%, respectively [16]. Autofluorescence imaging (AFI) can assess the lesion based on fluorescent intensity rather than analysis of surface pattern [17]. AFI with oral 5-aminolevulinic acid sensitization has incremental diagnostic yield compared to WLE [18]. Prospective randomized controlled trial (RCT) did not show any advantage of high definition


#### **Table 1.**

*Potential applications of various endoscopic imaging modalities in detection of ulcerative colitis associated neoplasia.*

chromoendoscopy (HDCE) guided targeted biopsy over HD-WLE guided random biopsies [19]. However, targeted biopsy may be cost-effective and time-saving [20]. An inter-observer agreement study has shown poor agreement on intention to biopsy among endoscopists in non-pedunculated potentially dysplastic lesions in UC [21]. Apart from IEE, EUS-guided assessment of depth of invasion can help in treatment selection [22].

#### **4. Dysplasia in ulcerative colitis and risk of advanced colorectal neoplasia (aCRN)**

#### **4.1 Low grade dysplasia**

Recurrent low-grade dysplasia (LGD) at first follow-up colonoscopy is a risk factor for aCRN as shown in a population-based registry from Netherlands with a hazard ratio of 1.66. A recurrence-free interval of three years predicts lower probability of subsequent occurrence of aCRN [23]. The risk of progression to aCRN is *Role of Interventional IBD in Management of Ulcerative Colitis(UC)-Associated Neoplasia… DOI: http://dx.doi.org/10.5772/intechopen.106599*

0.8% per year. Multifocal LGD, PSC, location in distal colon, and invisible uni-focal low-grade dysplasia are associated with disease progression and hence require colectomy [24]. However, this is not commonly practiced by clinicians with limited experience in surveillance colonoscopy and from non-academic centers [25]. A webbased prediction tool for progression of LGD to aCRN has been recently developed and validated based on these four parameters: endoscopically visible LGD >1 cm, unresectable/incomplete endoscopic resection, moderate/severe histologic inflammation within 5 years of LGD and multifocal LGD [26]. LGD in a case of primary sclerosing cholangitis (PSC) warrants colectomy as the risk of aCRN is considerably high after diagnosis of LGD in PSC (8.4 per patient-years) as compared to LGD in non-PSC patients (3.1 per patient-years). PSC is an independent risk factor for aCRN warranting annual colonoscopic surveillance [27]. Biopsy sampling of surrounding mucosa has limited yield in predicting risk of aCRN whereas the grade of dysplasia predicts aCRN [28].

#### **4.2 Indefinite dysplasia**

Indefinite dysplasia (IND) found in nearly 4% of patients can increase the risk of aCRN (3.1% per patient-years) by 6.9-fold after adjusting for other confounding factors [29]. On the other hand, post inflammatory polyps (PIP)/pseudo-polyps were predictive of higher severity of colonic inflammation and colectomy but not aCRN [30].

#### **4.3 Colonic strictures in UC**

Colonic stricture in ulcerative colitis was thought to be associated with neoplasia unless proven otherwise. However, strictures may represent inflammatory sequelae as well. Colonic strictures in long-standing colitis do not independently predict advanced colorectal neoplasia as shown in a retrospective cohort study mainly involving Crohn's colitis [31]. Prospective studies in ulcerative colitis-associated strictures are needed to confirm the finding. Non-passable strictures <4/5 cm on computed tomography (CT)-colonography without any evidence of dysplasia on endoscopic biopsy are candidates for endoscopic dilation [32].

#### **4.4 Non-conventional and invisible dysplasia**

A study retrospectively evaluating colonoscopic images recorded within last two years prior to diagnosis of UCAN has shown that the mean diagnostic delay for UCAN was nearly 15 months. Visible lesions were present in 25.9%, 18.2%, and 31.3% of UCAN, early- and late-stage cancers, respectively. Invisible lesions were more common in left colon and rectum and was associated with inflammation. UCAN with indistinct margins were more likely to be associated with inflammation than those with distance margins [33]. Two third of the non-conventional dysplasia in IBD (hypermucinous, goblet cell deficient and crypt cell dysplasia) can present with flat/ invisible dysplasia (crypt cell:96%, goblet cell deficient-65%, hypermucinous-42%) with equally high risk of subsequent aCRN (HGD or adenocarcinoma: 37% and 23% respectively in those with follow up colonoscopy; goblet cell>hypermucinous>crypt cell) [34]. These findings highlight the need for random biopsies in addition to targeted biopsies as non-conventional dysplasia often co-exist with the conventional dysplasia and can be the only form of dysplasia present. One-fifth of the dysplasias in IBD patients are found on random biopsies [35].

A recent study has highlighted that demarcated red-colored areas histologically characterized by increased vessel density and size (CD 34 positive) can be useful in identifying flat type dysplasia. These areas are common in base of LGD and throughout entire surface of HGD. Targeted biopsy from these areas should be considered [36]. In addition to Kudo's neoplastic pit patterns (III-V), pine-cone/villi pattern on surface morphology are highly specific for neoplasia and hence should be subjected to targeted biopsy [37]. Red in blue sign, pale-whitish mucosa, velvety appearance, ulceration, wall deformity, spontaneous friability and interruption of innominate grooves are signs of non-polypoidal UCAN [38].

#### **4.5 CRN in rectal stump post colectomy in UC**

Risk of CRN in rectal stump after ileorectal anastomosis (IRA) post-colectomy in UC is 7.1% and 14% after 10 and 20 years respectively. PSC, age at the time of IRA, UC disease duration and history of colorectal cancer are risk factors of CRN and rectal carcinoma after IRA. Hence ileal pouch anal anastomosis (IPAA) should be considered instead of IRA in high-risk patients such as PSC [39]. Acute severe UC decreases risk of IRA failure whereas Pre-colectomy thiopurine use within 12 months does not increase risk of CRN after IPAA in UC or indeterminate colitis [40].

### **5. Endoscopic resection of UCAN**

(**Figure 2**)

#### **Figure 2.**

*Algorithm for surveillance and management of ulcerative colitis associated neoplasia. HD-WLE- high-definition white light endoscopy, DCE- dye chromoendoscopy, VCE- virtual chromoendoscopy, CRC- colorectal cancer, FDR- first degree relative, H/o - history of, HGD- high grade dysplasia, LGD- low grade dysplasia, LST- laterally spreading tumor.*

*Role of Interventional IBD in Management of Ulcerative Colitis(UC)-Associated Neoplasia… DOI: http://dx.doi.org/10.5772/intechopen.106599*

#### **5.1 Endoscopic mucosal resection**

Earlier colectomy was indicated for any grade of dysplasia until it was recognized that endoscopy resection for polypoidal HGD or endoscopically visible dysplasia (earlier known as dysplasia-associated lesion or mass: DALM) with surveillance can avoid colectomy [41–44]. For polypoidal lesions, there was no difference between outcomes with polypectomy versus proctocolectomy. However, continued close surveillance is mandatory to identify metachronous lesions [45] Similarly it was realized that flat dysplasias can be managed safely with endoscopic mucosal resection (EMR) (**Figure 3** A-D)) [46]. Underwater EMR can be particularly beneficial in resecting UCAN compared to conventional EMR in areas of scarring and severe submucosal fibrosis (SMF) hindering lifting of the lesion [47]. UEMR is safe, effective and time-saving which have shown to remove large polyps in UC with submucosal fibrosis by "heatsink" and "floating" effects (**Figure 3** E-F) [48].

#### **5.2 Endoscopic submucosal dissection (ESD)**

For CAN, the en-bloc and Ro resection rates with ESD are 83% and 67%, respectively. However, a study reported that upto 70% can develop metachronous UCAN on long term follow up which may require colectomy or re-ESD according to a small study [49]. The advantage of ESD is total excision biopsy to evaluate the lesion. Compared to non-UC patients, ESD in UC is associated with lower rate of Ro resection (71% vs. 93%) with lower probability of negative horizontal margin [50]. Hence the demarcation line should be ascertained. Technical difficulties can occur due to scarring and excessive submucosal fibrosis (SMF) which can occur in nearly 40% of cases undergoing ESD [51]. Submucosal fatty infiltration is another limiting factor

#### **Figure 3.**

*Endoscopic mucosal resection (EMR) for ulcerative colitis associated neoplasia. A, B- flat visible dysplasias in a case of long-standing ulcerative colitis, C, D- EMR site post resection- biopsy showed high grade dysplasia, D, E- underwater EMR done for residual neoplasia post initial session of EMR.*

for ESD in UCAN [52]. Analysis of colectomy specimens have shown that 21% of the lesions can be invisible endoscopically highlighting the importance of intensive surveillance colonoscopy [51]. To overcome the effect of SMF, multi-traction technique using three intertwined loops with clips have been used to treat recurrence of HGD in UC [53]. Another study in 133 colorectal neoplasms (28 with UC) with submucosal fibrosis (28 had UC) water pressure assisted ESD (WP-ESD) had significantly shorter procedure time related to conventional ESD [54].

In a meta-analysis of 203 dysplastic lesions (mean size 2.7 cm, 83% left colon, 90% non-polypoid,) in 192 UC patients, the en bloc resection, complete resection, and R0 resection rates were 94%, 84%, and 81% respectively. SMF was seen in 71%. Mean procedure time was 83 minutes. The rates of local recurrence, metachronous tumor and additional surgery were 5%, 6%, and 10% respectively. Adverse events like bleeding and perforation were seen in 8% and 6%, respectively [55]. Another systematic review showed comparable en bloc and R0 resection rates (88.4% and 78.2% respectively) [56]. Results of ESD in UCAN is best for those with non-invasive pit/vascular pattern, no surface ulceration, distinct borders and appropriate lifting on submucosal injection [57]. Results of ESD for non-polypoidal UCAN is inferior to those for polypoidal lesions due to SMF in 90−100% patients: en-bloc and curative resection rates are 60−100% and 70−79% respectively. Adverse events and recurrence occurred in <10% and 4−20% respectively [58–60].

Prior to widespread use of ESD, endoscopic piecemeal resection followed by argon plasma coagulation had been described in the past for large, poorly lifting adenomas [61].

#### **5.3 Choice of an endoscopic resection technique in UCAN**

The choice between ESD and EMR for UCAN can be decided based on a recent study which showed that ESD has higher R0 resection rates than EMR for ≥11 mm lesions (94% vs. 55%) and non-polypoidal lesions (100% vs. 55%). Hence it was concluded that EMR can be preferred for lesions ≤10 mm. 10% patients had intra-procedure perforation during ESD and metachronous HGD noted in 3% [62]. Another study concluded that EMR is indicated for small lesions without fibrosis and ESD for large lesions with fibrosis [63]. Overall, it is important to note that endoscopic resection techniques can help in preventing colectomy by removal of large CRNs [64].

#### **5.4 Modalities other than EMR or ESD**

Hybrid resection with ESD and FTRD can be useful in lesions with severe submucosal fibrosis. Hybrid ESD can be useful in large laterally spreading tumor [65]. ESD assisted EMR had been described as early as in 2008 in a series of 67 patients, which reported en-bloc resection rate of 78% with R0 resection rate of 94% in those undergoing en-bloc resection [66]. A recent report first described use of FTRD in a case of long-standing UC for a non-lifting, fibrotic adenoma in descending colon [67].

#### **5.5 Risk of recurrence**

The chance of recurrence of cancer and any dysplasia after endoscopic resection of polypoid dysplasia in UC are 5.3 cases/1000 patient-years and 65 cases/1000 patientyears, respectively [68].

*Role of Interventional IBD in Management of Ulcerative Colitis(UC)-Associated Neoplasia… DOI: http://dx.doi.org/10.5772/intechopen.106599*

#### **Figure 4.**

*Management algorithm for endoscopic management of complications after ileal pouch anal anastomosis. HGDhigh grade dysplasia, LGD- low grade dysplasia.*

#### **6. Role of IIBD in postoperative pouch complications in UC**

Among pouch related complications, pouch strictures, floppy pouch complex, acute and chronic anastomotic leak or sinuses can be amenable to endoscopic therapy (**Figure 4**) [69].

#### **6.1 Pouch strictures**

Pouch outlet stricture related to sealed ileal pouch have been treated with wire guided stricturotomy using insulated tip (IT) knife [70]. Pouch strictures (inlet and outlet) can be successfully dilated with controlled radial expansion (CRE) balloon relieving symptoms, restoring pouch patency and improved quality of life in a study by Shen et al. of 19 patients with pouch strictures (11 had Crohn's disease of the pouch) [71]. The clinical success of endoscopic balloon dilation (EBD) is 66.7% as reported in a study by Kirat et al. with rest requiring excision of pouch. Nearly half require repeat EBD. Pouch inlet/afferent limb strictures can be treated effectively with both EBD and endoscopic stricturotomy (ES) with comparable surgery free survival as shown by Lan et al. (160 EBD, 40 EST) [72]. The risk of bleeding is higher with ES (4.7% vs. 0% with EBD) whereas the risk of perforation is higher with EBD (0.8% vs. 0% with ES). Length of stricture (>5 cm) and pouchitis are predictors of subsequent surgery [72]. Another study reporting 88 dilations in 20 patients (majority 87% had ileo-anal anastomotic strictures, 95% had UC) showed a technical and clinical success of EBD as 98% and 95% respectively without any major adverse events. The study hence concluded that EBD should be the first line for pouch strictures [73]. In the largest study of 150 patients undergoing 646 EBD procedures, perforations and bleeding occurred in less than 1% cases. At a median follow up of nearly 10 years, 87.3% retained their pouches. Multiple strictures and Crohn's disease of the pouch were independent predictors of pouch failure [74].

#### **Figure 5.**

*Endoscopic management of pouch strictures. A. Ileal pouch anastomotic stricture, B. endoscopic balloon dilation (EBD) being performed, C. stricture post EBD, D. Pouchitis noted in ileal pouch post anastomotic dilation, E. pouch inlet stricture, F. EBD for pouch inlet stricture.*

Based on results of various studies, a systematic review has concluded that for pouch anal strictures, bougie dilation followed by balloon dilation (**Figure 5** A-D) are the modalities prior to surgical dilation. Endocarp guided needle knife stricturotomy is another alternative approach [75]. Pouch inlet strictures need to be treated with both medical (for inflammatory stricture) and endoscopic therapy (EBD) (for fibrotic stricture) (Figure E-F) [75]. Mid pouch stricture has been treated with surgical stricturoplasty rather than excision of pouch [75].

#### **6.2 Pouch leaks**

Successful management of leak from the "tip of the J" have been described with two over the scope clips (OTSCs) [76]. OTSCs have been shown to be successful in nearly two thirds of the patients with one or two sessions in closing such leaks while remaining require revision surgery. 50% patients required re-procedure (OTSC clip or endoscopic suturing) and finally one third required surgery [77]. Apart from direct closure of defects, a short period of endoscopic vacuum therapy (EVT) with periodic sponge changes can help in early surgical closure for treating anastomotic leakage post IPAA. 100% secondary anastomotic healing (median healing time 48 days) was achieved in early closure group (n = 15) compared to 52% (median healing time 70 days) in conventional treatment group (n = 29) [78]. In another series of 8 patients, complete healing of leak was documented in median 2 months-time [79]. Hence EVT can be used for anastomotic leak post IPAA whereas OTSC is to be used if there is leak without any abscess [7].

#### **6.3 Pouch fistula**

Endoscopic fistulotomy can be used in short (< 3 cm), superficial (<2 cm thick), simple fistulas like pouch-to-pouch body fistula, perianal fistula and ileo-cecal fistula *Role of Interventional IBD in Management of Ulcerative Colitis(UC)-Associated Neoplasia… DOI: http://dx.doi.org/10.5772/intechopen.106599*

[7]. In a study of 29 patients (26 IPAA, 21 having UC) with IBD related fistulas, endoscopic fistulotomy (EFT) with needle knife was successful in healing fistula in nearly 90% patients whereas 10% require surgical intervention [80]. Preliminary results of another study comparing EFT with redo-surgery showed complete healing in all cases of redo surgery with complete and partial fistula healing in 78.4% and 21.6% wire EFT respectively. Rate of subsequent surgery and adverse events were lower in EFT arm (n = 40) compared to redo surgery (n = 19) [81]. Combined use of multiple sessions of endoscopic clipping and EFT have been used to completely heal pouch-to-pouch fistula from tip of the "J" to the anastomosis [82].

#### **6.4 Pouch sinus**

Endoscopic sinusotomy can be successfully used to manage chronic pouch anastomotic sinus after IPAA in UC with fair healing rate (53.2% complete, 15.3% partial) as compared to 94% initial complete healing rate with redo surgery as shown in a historical cohort study (endoscopic sinusotomy 141, surgery 85). However, redo surgery was associated with higher morbidity (43.5%) vs. compared to endoscopic sinusotomy (2.5%). Subsequent recurrence and need for surgery were not significantly higher in endoscopic arm as compared to surgical closure [83]. Like pouch fistulas, EVT can be helpful in treating anastomotic leak post IPAA preventing development of chronic pre-sacral sinus [84]. Multiple sessions of endoscopic sinusotomy under doppler ultrasound guidance have been used along with topical doxycycline (100 mg IV with 10 ml saline) (a matrix metalloproteinase inhibitor which promote fibrosis) injection for refractory sinus post IPAA [85]. However, endoscopic therapy is reserved for small sinus tracts whereas surgery may be required for large, deep symptomatic sinuses [86].

Few studies have evaluated factors influencing sinus healing and pouch survival with endoscopic sinusotomy. Crohn's disease of the pouch is a negative predictor of pouch healing whereas higher BMI and longer intervals between sinusotomy were positive predictors [87]. Conversely, another study by the same group have shown that excess BMI gain (≥ 10%) post sinusotomy was associated with recurrent sinus [88]. With regard to surgery free survival, acute anastomotic leak, toxic megacolon, longer sinus and delayed sinusotomy were risk factors; whereas longer interval between sinusotomies, concurrent 50% dextrose and doxycycline use were protective factors [87]. Endoscopic hemostasis for severe bleeding in diverted ileal pouch have been described with spray of hypertonic saline (50% dextrose) [89]. Incremental number of endoscopic sinusotomy increase the chances of sinus healing whereas delay in sinus diagnosis and complex sinuses are negative predictors of success as shown in another study of 65 patients [90].

#### **6.5 Floppy pouch complex**

Floppy pouch complex is managed initially with lifestyle modifications like avoidance of excessive straining failing which endoscopic ligation/plication can be considered [69].

#### **6.6 Pouch neoplasia**

Low grade dysplasia, high grade dysplasia, adenocarcinomas and squamous cell carcinomas are reported to occur in pouch after IPAA. Presence of established (pre-colectomy cancer or dysplasia) and proposed risk factors (PSC, family history of colon cancer, chronic pouch inflammation, long standing UC, type "C" mucosa- atrophic mucosa with chronic inflammation) predict risk of pouch neoplasia and direct pouch surveillance [91]. Presence of established risk factors warrant annual surveillance pouchoscopy with at least 3 biopsies from cuff/anal transition zone, pouch inlet and body or any endoscopically visible lesion [2]. Presence of proposed risk factors warrant pouchoscopy with biopsy every 1−3 years. Surveillance pouchoscopy is recommended every 3 years in patients without risk factors [2]. Surveillance is important given the fact that pouch neoplasia has poor prognosis and early detection can salvage pouch. After endoscopic resection of uni-focal polypoidal/raised LGD by polypectomy/EMR/ESD, surveillance should be done every 3 months for 2 years. Irrespective of the modality of endoscopic resection (EMR/ESD), the resection should be en-bloc with extensive biopsy of adjacent mucosa. Multifocal/flat/persistent LGD, HGD or pouch cancer should be treated with surgical intervention (excision, mucosectomy or pouch advancement). People with established risk factors of pouch neoplasia may require complete proctectomy [91] .

#### **7. Conclusion**

The role of interventional endoscopy in diagnosis and management of ulcerative colitis associated neoplasia and pouch complications post colectomy in UC are expanding. While HD-WLE and CE are established methods of screening for UCAN, other modalities of virtual CE are emerging. Endocytoscopy and pCLE have the potential for "in vivo" diagnosis of dysplasia. EMR, ESD and recently FTRD have been employed for endoscopic resection of UCAN. Underwater EMR and traction or water pressure assisted ESD can help in resecting UCAN in the presence of submucosal fibrosis. Among pouch related complications, pouch strictures, leaks, fistula, sinus, pouch neoplasia and floppy pouch can be managed endoscopically. Future prospective and comparative studies are required to further define the role of IIBD in the current management algorithm of UCAN and pouch complications.

#### **Authors' contribution**

**Concept and design:** PP; **Administrative support:** MT, DNR; **Provision of study material/patients:** PP; **Acquisition of data:** PP. **Data Analysis and interpretation:** PP; **Preparation of initial draft:** PP,; **Critical revision of the manuscript:** MT, RB, DNR, **Important intellectual inputs and revision:** MT, RB, ZN, MR, DNR **Manuscript writing:** All authors, **Approval of final manuscript:** All authors.

*Role of Interventional IBD in Management of Ulcerative Colitis(UC)-Associated Neoplasia… DOI: http://dx.doi.org/10.5772/intechopen.106599*

#### **Author details**

Partha Pal\*, Rupa Banerjee, Mohan Ramchandani, Zaheer Nabi, Duvvuru Nageshwar Reddy and Manu Tandan Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India

\*Address all correspondence to: partha0123456789@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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### *Edited by Partha Pal*

Ulcerative colitis (UC) is one of the major forms of inflammatory bowel disease (IBD). Epidemiological trends suggest an initial rise in the incidence of UC, followed by Crohn's disease (CD), in areas where IBD is emerging. As understanding of aspects of the disease is evolving, this book covers new perspectives on the etiology, clinical manifestations, diagnosis, and management of UC. Genetic predisposition, along with gut dysbiosis and environmental factors, triggers the altered gut permeability and dysregulated immune activation that leads to the development of UC, which can manifest both intestinally and extra-intestinally. Platelets play a significant role in augmenting inflammation. Histological examination is important for accurate diagnosis and for distinguishing mimics. Histological remission is an emerging treatment target strategy in UC. Novel treatments include dietary manipulation with anti-inflammatory dietary components like fermented rice bran. A number of challenges need to be addressed in treating special populations like children and pregnant women. Finally, interventional endoscopy is playing an emerging role in the management of colitis-associated neoplasia and postoperative complications and acting as a bridge between surgery and medical therapy. *Ulcerative Colitis - Etiology, Diagnosis, Diet, Special Populations, and the Role of Interventional Endoscopy* aims to act as a ready reference for the clinician. It provides indispensable updates on several relevant issues in the diagnosis and management of ulcerative colitis and has benefited from the collaboration of leading experts in various aspects of the disease. It aims to facilitate decision-making by gastroenterologists, IBD specialists, interventional endoscopists, dieticians, pathologists, surgeons, and pediatricians treating UC patients.

Published in London, UK © 2022 IntechOpen © selvanegra / iStock

Ulcerative Colitis - Etiology, Diagnosis, Diet, Special Populations, and the Role of

Interventional Endoscopy

Ulcerative Colitis

Etiology, Diagnosis, Diet, Special Populations,

and the Role of Interventional Endoscopy

*Edited by Partha Pal*