Diagnosis of Pouch Disorders: Endoscopy

Chapter 15

Diagnosis of Pouch Disorders: Endoscopy Bo Shen, MD Center for Inflammatory Bowel Diseases, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, United States

ABBREVIATIONS ACD anemia of chronic disease AImD autoimmune disorders AInD autoinflammatory disorders ALS afferent limb syndrome ATZ anal transitional zone BCIR Barnett continent intestinal reservoir CAN colitis-associated colitis CARP chronic antibiotic-refractory pouchitis CD Crohn’s disease CMV cytomegalovirus CT computed tomography EGD esophagogastroduodenoscopy ELS afferent limb syndrome EUS endoscopic ultrasonography FAP familial adenomatous polyposis GI gastrointestinal IDA iron deficiency anemia IMP immune-mediated pouchitis IBD inflammatory bowel disease IPS irritable pouch syndrome LI loop ileostomy IL interleukin MH mucosal healing MRI magnetic resonance imaging NSAID non-steroidal anti-inflammatory drugs OCT optical coherence tomography PDAI the Pouchitis Disease Activity Index PSC primary sclerosing cholangitis PVF pouch-vaginal fistula TNF tumor necrosis factor UC ulcerative colitis VCE video capsule endoscopy

INTRODUCTION There is a long list of pouch or pouch-related disorders. Fortunately, all most all pouch disorders are located at the perianal area, cuff, anal transitional zone (ATZ), pouch body, and afferent limb. Those anatomic structures are easily reached with a regular upper endoscope. Pouch endoscopy or pouchoscopy plays a critical role in diagnosis, differential diagnosis, disease monitoring, dysplasia surveillance, and therapy of pouch disorders. The role of pouchoscopy in the diagnosis of Pouchitis and Ileal Pouch Disorders. https://doi.org/10.1016/B978-0-12-809402-0.00015-0 © 2019 Elsevier Inc. All rights reserved.

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pouchitis and other pouch disorders has several folds: (1) evaluation of the distribution of inflammation; (2) evaluation of inflammatory and structural abnormalities of the pouch; (3) quantification of inflammation of each topographic locations of the pouch (afferent limb, pouch body, and ATZ; (4) monitoring of disease activity and assessment of response to medical, endoscopic, and surgical treatment; and (5) surveillance for neoplasia. In addition, pouchoscopy provide a route for the delivery of endoscopic therapy. The evaluation of some pouch or pouch-associated disorders may require other endoscopic modalities, such as upper endoscopy, ileoscopy, capsule endoscopy, and image-enhanced endoscopy.

ANATOMY AND LANDMARKS OF THE ILEAL POUCH The most common ileal pouch configurations are the J-pouch, S-pouch, Kock pouch, and Barnett continent intestinal reservoir (BCIR). The J- and S-pouches are categorized as pelvic pouches; and Kock pouch and BCIR as abdominal pouches or continent ileostomies. There are four approaches for the construction pelvic pouch: (1) stapled anastomosis without mucosectomy; (2) stapled anastomosis with mucosectomy; (3) handsewn anastomosis without mucosectomy; and (4) handsewn anastomosis with mucosectomy. The #1 and #3 are most commonly performed (Fig. 15.1). Each pouch configuration has some unique landmarks. The recognition of those landmarks is important for the endoscopic diagnosis and therapy. Since the majority of pouch disorders are located at the distal afferent limb, pouch body, and outlet area, it is important to push the endoscope to the bowel segment beyond previous loop ileostomy (LI) site. The anatomic structure around pouch-anal anastomosis, albeit being short, is complicated, which includes anus or anal verge, dentate line, anal valve, anal column, ATZ, and rectal columnar cuff. The anatomy in the pouch is illustrated by an artist’s illustration (Fig. 15.2), surgical resection specimen (Fig. 15.3), and endoscopy (Fig. 15.4). A well-constructed pouch should have straight pouch lumen without twist, excessive dilation, folding, angulation, or prolapse (Fig. 15.5).

J-Pouch The J-pouch body is made from the conjunction of two limbs of the distal small bowel. The body of a J-pouch has one “U” turn at the distal pouch, conjoining the afferent limb and efferent limb sides. The normal size of a J-pouch is proximately 15–18 cm long. An excessively long J-pouch body can cause angulation and twist, resulting in bowel obstruction and patient’s symptoms of bloating and dyschezia (Fig. 8.16). Occasionally, linear superficial ulceration can be seen along the vertical staple line or suture line, which may result from ischemia and be consider as being normal (Fig. 15.6B). Attempt to take biopsy from the ulcerated staple line should be avoided to minimizing confusion between resulted foreign-body granulomas and Crohn’s disease (CD)-associated granulomas. The efferent limb of the pouch body ends with an anatomic area called the tip of “J”. The tip of “J” area is stapled with or without strengthening of the omentum. The staple(s) or sutures may be visible on endoscopy (Fig. 15.7A and C). This area may be ulcerated or nodular, which can be “normal” or part of pathology (Fig. 15.7B). The tip of the “J” is a common

FIG. 15.1  Common configurations of pelvic pouches. (Courtesy of Mr. Joe Pangrace of Cleveland Clinic.)

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Afferent limb Pouch inlet Tip of the “J” Efferent limb

Columnar cuff Anal rectal ring Anal transitional zone Anal columns Surgical anal canal

Anatomic anal canal

Dentate line Anal verge or anus

FIG. 15.2  Anatomy of J-pouch outlet. (Courtesy of Mr. Joe Pangrace of Cleveland Clinic.)

Pouch body

Anastomosis Rectal cuff with cancer Anal transitional zone Anal columns Dentate line Anal verge

FIG. 15.3  Anatomy of ileal pouch-anal anastomosis shown here resected pouch for cancer at the cuff. Photo courtesy of Dr. Victor Fazio.

location of suture line or staple line leak, which can be detected with a soft-tip guide wire via endoscopy as well as contrasted pouchogram or MRI (Fig. 15.7D). The J-pouch body has the inlet connecting the proximal small bowel (i.e., neo-terminal ileum, also called afferent limb) and outlet linking to the rectal stump or ATZ. In a well-constructed J-pouch, there is an owl’s eye configuration at the proximal pouch body, with one eye being the pouch inlet and the other being the tip of the “J” and the beak being the ridge between the afferent and efferent limbs of pouch body (Figs. 15.5A and 15.8A) [1]. Various disease c­ onditions

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FIG. 15.4  Normal pouch outlet. (A) Stapled anastomosis without mucosectomy with rectal cuff (green dot line); (B) handsewn anastomosis with a short anal transitional zone (yellow dot line); (C) normal cuff on retroflex view with dentate line (green arrow) and anal columns (yellow arrow); (D) squamous patch at the anal transitional zone, easily mistaken as ulcers.

can lead to distortion of the “owl’s eye” configuration, such as pouch ischemia, CD of the pouch, and ischemia. In fact, the loss of the “owl’s eyes” configuration has been shown to be associated with a high risk for pouch failure (Figs. 15.5 and 15.8) [1]. The construction of a J-pouch is typically in conjunction with stapled anastomosis without mucosectomy. A 2–2.5 cm rectal cuff remains. An excessively long cuff may cause problems later on, such as efferent limb syndrome (ELS) from the angulation between the pouch body and the long cuff and proctitis (Fig. 8.19). A very short cuff may be prone to the development of anastomotic or anal stricture or even fistula. The ATZ is typically short in patients with surgical redo pouches (Fig. 15.9A). For technical reason, occasionally ileal pouch-rectal anastomosis is constructed to avoid the anastomotic tension (Fig. 15.9B). Sometimes, dislodged staples, especially those in the anterior wall, can cause discomfort, which can be endoscopically removed (Fig. 15.9C). Anastomotic stricture is common, which has been treated with endoscopic balloon dilation, endoscopic stricturotomy, or self-catheterization or bougie dilation. Repeated self-catheterization or bougie dilation can result in mucosal inflammation (Fig. 15.9D). Afferent limb should be clear from inflammation. However, medications [such as nonsteroidal anti-inflammatory drugs (NSAIDs), ischemia, autoimmune enteritis and pouchitis, and CD] can cause different pattern of enteritis above the pouch inlet (Fig. 15.10). Endoscopy should reach the bowel segment beyond the previous stoma site, as there are unique anatomies and disorders (such as stricture at the end-to-end anastomosis) and dilated bowel lumen at the side-to-side anastomosis) in the area (Fig. 15.11).

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FIG. 15.5  Normal and abnormal pouch body. (A) Normal sized straight pouch with “owl’s eye” configuration; (B) contracted pouch; (C) mega pouch; (D) twisted pouch.

S-Pouch The choice of construction of an S-pouch is largely based on the technical requirement. One of the major challenges for constructing a J-pouch is the issue of “reach”, since the small bowel-converted ileal pouch body is an abdominal organ with a limited length of mesentery to reach the rectal stump, especially in obese patients or in those with deep, narrow pelvis. The construction of an S-pouch would give an additional 2–3 cm of the small bowel to reach the rectal stump. Structurally, an S-pouch consists of three limbs or two “U” turns, as compared to the two-limb, one-“U” turn J-pouch. Therefore, the pouch volume of an S-pouch is larger that of a J-pouch. The S-pouch does not have the tip of the “J” or the “owl’s eye” configuration. The junction between the afferent limb and the S-pouch body is prone to the development of angulation, causing ELS. Endoscopist may find it difficult to intubate the area (Fig. 8.14). Similar to the J-pouch, the afferent limb of the S-pouch body continues from the neo-terminal ileum or afferent limb via the pouch inlet. However, the efferent limb of the S-pouch continues distally till reach the anastomosis. The efferent limb segment outside pouch body should be around 2 cm. An excessively long efferent limb of the S-pouch can lead to ELS with obstructive defecation (Fig. 8.15).

Kock Pouch Kock pouch is the most commonly constructed continent ileostomy, The primary Kock pouch remains to be a valid surgical option for patients who would otherwise eligible for a pelvic pouch, but have a history of anal sphincter injury or poor anal sphincter function. In the secondary K-pouch is defined as a rescue operation for highly selected patients with failed J- or S-pouches [2].

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FIG. 15.6  Normal and abnormal mid pouch staple line. (A) Thin and clean staple line; (B) ischemic ulcer along the staple line; (C) deformed inlet, tip of the “J”, and staple line resulting from Crohn’s disease; (D) fistula track beneath the staple line, detected with a guide wire.

The anatomic structures of a Kock pouch consist of a nipple valve across the abdominal wall, pouch body, pouch inlet, and afferent limb. The health of a Kock pouch largely depends on the structure and function of the nipple valve. The ­endoscopist should perform a retroflexion to assess the shape, length, and base of the valve for the slippery, ulceration, and fistula. The most common locations of pouch strictures are at the pouch inlet and nipple valve. The healthy and diseased Kock pouch conditions are detailed in Chapter 38.

Barnett Continent Intestinal Reservoir BCIR is a variant of Kock pouch, which has been created with an intention to strengthen the valve. The anatomy of BCIR therefore resembles to that of the Kock pouch, except the presence of a loop of bowel around the base of the valve. The healthy and diseased BCIR conditions are detailed in Chapter 38.

Ileostomy The creation of an end ileostomy and/or LI is a part of staged ileal pouch surgery. Typically, the end ileostomy is constructed, following subtotal colectomy and Hartmann procedure and setting up subsequent pouch procedures. End ileostomy is also performed for permanent fecal diversion after pouch failure. The LI is routinely constructed after IPAA procedure, with anticipation of stoma closure within 2–4 months. LI is closed with end-to-end or side-to-side anastomosis, which creates an anastomotic structure, 10–25 cm above the pouch inlet (Fig. 15.11). Stricture at the site of end-to-end anastomosis can occur (Fig. 15.11C and D), while the lumen of side-to-side anastomosis if often dilated (Fig. 15.11A and B). In patents with dilated pouch body and afferent limb, the LI site may be mistaken as the pouch inlet.

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FIG. 15.7  Normal and abnormal tip of the “J”. (A) Staple; (B) ischemic ulcers; (C) ulceration along the staple line; (D) a chronic leak.

Diverted Pouch In the staged pouch surgery, a newly constructed pouch requires temporarily diverted, while a failed pouch may need permanent diverted. The diverted pouch may have a various degree of inflammation (i.e., diversion pouchitis) and sometimes may have distal pouch stricture.

PREPARATION AND PRECAUTION FOR POUCH ENDOSCOPY Sedated or non-sedated diagnostic pouchoscopy can be safely performed in an outpatient setting. Topical sodium phosphatebased enemas immediately before procedure or oral polyethylene glycol-based solution at previous night are adequate for bowel preparation. For sedated pouchoscopy, at least 6-hour fasting is needed. Due to the absence of the accommodative colon, patients with an ileal pouch have a poor tolerance of air insufflation. Therefore, carbon dioxide insufflation is preferred. Different segments of the ileal pouch need to be carefully examined and photo documented. In general, the depth of intubation of the pouchoscope is at least beyond the level of the previous LI site. If a prolonged pouchoscopy with an excessive insufflation is performed, decompression with the insertion of a nasogastric tube to the pouch body at endoscopy recovering room has been helpful to reduce post-procedure associated bloating or ileus. Tissue biopsy is routinely performed for the diagnosis and surveillance purpose. Caution for bleeding should be taken in patients with concurrent primary sclerosing cholangitis (PSC), due to portal hypertension and thrombocytopenia. This author has been using 50% dextrose spray to control biopsy-associated bleeding (Fig. 15.12). Patients suspected of stricture, anastomotic leak, sinus, or abscess, abdominal, and pelvic imaging such as MRI, CT, gastrografin enema, and barium defecography should be performed before the endoscopy. It is recommended, however, that the same-day pouchoscopy following peroral contrasted abdominal imaging be avoided for the risk of aspiration. When performing pouchoscopy, the endoscopist should keep orientation in mind. In the left-lateral supine position, the posterior wall of the pouch body or anastomosis is at 10–11 o’clock; and the anterior wall is at 4–5 o’clock. Adjacent to the

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FIG. 15.8  Normal and abnormal pouch inlet. (A) Normal inlet with the “owl’s eye” configuration; (B) afferent limb syndrome (angulation at the inlet); (C) inlet stricture; (D) inlet polyps.

posterior wall is scrum or presacral space and adjacent to the anterior wall is the vagina or prostate and bladder. With the correct orientation in mind, the endoscopist will be able to search for targeted location of the disorders, such as presacral sinus at the posterior wall and pouch-vaginal fistula (PVF) and distal prolapse, at the anterior wall.

POUCHOSCOPY IN DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS Pouchitis is the most common long-term adverse sequelae for IPAA. The most common symptoms of pouchitis are increased bowel frequency, loose or watery stool, abdominal cramps, urgency, and nocturnal seepage. However, those symptoms are not specific which can occur in other inflammatory, structural and functional disorders of the pouch, such as pouch sinus, pouch stricture, CD of the pouch, cuffitis, and irritable pouch syndrome (IPS). Objective assessment of diseased conditions of the pouch is the key. Pouchoscopy is the most important modality for the diagnosis and differential diagnosis of pouchitis and ileal pouch disorders.

Pouchitis The role of endoscopy in the assessment of pouchitis is demonstrated in the following aspects: (1) diagnosis by the measurement of disease activity; (2) monitoring of disease activity and response to medical, endoscopic, or surgical therapy; (3) assessment of distribution of inflammation, which may provide clue for the etiology of pouchitis; and (4) mucosal biopsy for diagnosis, differential diagnosis, and dysplasia surveillance. Based on the different criteria, pouchitis is classified into categories and phenotypes. The proposed classification of pouchitis and ileal pouch disorders is detailed in Chapter 8. Briefly, pouchitis can be divided into: (1) acute vs. chronic with cut off of duration symptoms of 4 weeks; (2) idiopathic vs. secondary, based on the presence or absence of etiological or triggering factors such as infections with pathogens [Clostridium difficile [3, 4], cytomegalovirus (CMV) [5], Campylobacter

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FIG. 15.9  Variants of cuff and anal transitional zone. (A) A short anal transitional zone in patient with pouch redo; (B) ileal pouch-rectal anastomosis with a long “cuff”; (C) dislodged staple at the anastomosis; (D) “cuffitis” from repeat trauma of self-intubation for anastomosis stricture.

jejuni [6], and Candida albicans [7], the use of NSAID], and ischemia; (3) relapsing vs. non-relapsing pouchitis; and (4) antibiotic responsive vs. antibiotic dependent vs. antibiotic refractory, based on the response and requirement of antibiotic therapy. In clinical practice, a combination of the classification systems has been used, for example the definition and common use of the term, “chronic antibiotic-refractory pouchitis” (CARP). Furthermore, we have proposed that pouchitis can be divided into three broad categories based on the speculated etiology and pathogenesis: (1) microbiota-related, including dysbiosis-associated and pathogen-associated; (2) immune-mediated; and (3) ischemia or surgical technique related. Moreover, immune-mediated pouchitis (IMP) encompasses a broad category of disease processes. To date, IMP can be subclassified in to PSC-associated pouchitis, IgG4-associated pouchitis, autoimmune disorder (AImD)-associated pouchitis, and autoinflammatory disorder (AInD)-associated pouchitis [8, 9]. Since the treatment of those phenotypes of pouchitis is quite different, proper diagnosis of each of the disease category is critical. However, endoscopic observation alone may not be sufficient for the diagnosis, classification, and subclassification may not be adequate. A combined assessment of hematoxylin-eosin-based histology and immunohistochemistry (such as CMV immunohistochemistry), and laboratory tests (such as C. difficile toxins) is often needed. Endoscopic assessment is a required for the diagnosis of pouchitis. There are several diagnostic instruments to quantify the degree of inflammation of the pouch with endoscopic degree of inflammation as the most important component. The typical endoscopic features of pouchitis are edema, erythema, granularity, nodularity, loss of vascular pattern, mucus exudates, friability, hemorrhage, ulceration, and inflammatory pseudopolyps. The currently available diagnostic instruments in pouchitis are discussed in Chapter 17. The most commonly used is the 18-point Pouchitis Disease Activity Index (PDAI), which consists of symptom (0–6 points), endoscopy (0–6 points), and histology (0–6 points) subscores. A PDAI score greater than or equal to 7 points is considered as being diagnostic for pouchitis [10]. The PDAI endoscopy subscores consist of 6 items: edema, granularity, friability, loss of vascular pattern, mucosa exudates, and ulcers (Fig. 15.13). The PDAI

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FIG. 15.10  Normal and abnormal afferent limb. (A) Normal afferent limb; (B) ischemic segment at the distal afferent limb with a sharp demarcation from normal segment; (C) diffuse enteritis along with pouchitis, associated with primary sclerosing cholangitis; (D) Crohn’s ileitis with discrete ulcers above the site of ileostomy.

instrument has suffered from its inherent drawbacks, such as the lack of weighed items. For example, the presence of ulcer should be weighed more than edema. Furthermore, there is a spectrum in the severity of ulcers, ranging from aphthous to deep serpiginous. The ulcer can be aphthous, small or large, round, linear or confluent, shallow or deep, and diffusely and focally distributed (Fig. 15.14). However, whether the number, shape, depth, and location of the ulcers are associated with the long-term disease course, response to treatment, disease recurrence, or prognosis is not clear. More objective disease activity instrument is under development in an international joint collaboration [11]. The instruments explored endoscopic items in existing indices, including granularity and nodularity, the presence or absence of bleeding, contact vs spontaneous bleeding, vascular pattern, mucopurulent exudate, erosions, ulcerations, erythema, and mucosal hemorrhages. The investigators further explored items, including stenosis, location of stenosis (pouch body or inlet), sinus, fistula, and affected surface in pouch body. Substantial reliability was observed only for the endoscopic items of ulceration and ulcerated surface in the pouch body which was correlated with a global evaluation of lesion severity [11]. Endoscopy has been routinely used in monitoring disease activity in pouchitis as well as in inflammatory bowel disease (IBD). Endoscopic mucosal healing (MH) has been extensively used in clinical trials in CD and UC as one of the primary outcomes. MH has increasingly been used in clinical practice in IBD in general. The PDAI or modified PDAI [12], with endoscopy subscores as one of main components, have been used in clinical trials [13, 14]. However, there is no consensus on the definition of MH in patients with inflammatory disorders of the pouch. In addition, there are limited published data on MH in monitoring disease and assessment of treatment outcome in pouchitis. Fecal markers such as calprotectin [15] and lactoferrin [16] has been studied in patients in the ileal pouch, in correlation with mucosal inflammation. In a longitudinal study the fecal markers have been shown to be useful for the prediction of pouchitis after IPAA [17]. One of the challenges is that “normal” ulceration in the suture or staple lines may cause an elevation of those biomarkers. The endoscopic assessment of distribution of inflammation is important for the diagnosis and subclassification of pouchitis. Microbiota-associated pouchitis typically presents homogeneous, diffuse inflammation with or without ulcers in the

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FIG. 15.11  Side-to-side versus end-to-end anastomoses at the site of loop ileostomy closure. (A) Dilated lumen at the side-to-side anastomosis; (B) a small diverticulum at the side-to-side anastomosis; (C) strictures are common at the end-to-end anastomosis; (D) endoscopic stricturotomy and clipping of stricture.

FIG. 15.12  Risk of bleeding associated with biopsy in patients with portal hypertension. (A) bleeding after surveillance cuff biopsy in primary sclerosing cholangitis; (B) bleeding controlled by spray of 50% dextrose.

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FIG. 15.13  The 6 components of the Pouchitis Disease Activity Index endoscopy subscores. (A) Edema; (B) granularity; (C) friability (bleeding from scope passage); (D) loss of vascular pattern; (E) mucosa exudates; (F) ulcers.

FIG. 15.14  Pattern of pouch ulcers. (A) Erosions or aphthous ulcers; (B) small ulcers; (C) linear ulcers along staple line from ischemia; (D) multiple diffuse ulcers; (E) large ulcer; (F) confluent ulcers.

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pouch body (Chapter 8 and Fig. 8.26). Few patients may have a short segment (<10 cm) of “backwash ileitis”. In contrast, the inflammation of IMP often involves both pouch body and a long segment of >10 cm of the afferent limb, sharing a similar pattern of inflammation. Some patients with IMP may also have concurrent cuffitis (Fig. 8.27). In fact, a similar pattern of mucosal inflammation of IMP may be seen in the proximal small bowel, particularly at the duodenum. This phenomenon supports the notion that IMP may be a “disease of system,” not being limited to the pouch. Ischemic pouchitis is newly described disease category, which is characterized by the unique pattern of the distribution of inflammation on endoscopy (Fig. 8.28). The risk factors for ischemic pouchitis including male gender, obesity, the presence of J-pouch (vs. S- or K-pouch), history of thromboembolic disease, and multiple subsequent abdominal or pelvic surgeries after the pouch operation. The endoscopic features include inflammation with or without ulceration limited only to one limb (commonly at the efferent limb side of the pouch body) with a sharp demarcation of inflamed and non-inflamed parts along the staple line [18]. Occasionally, ischemic pouchitis may present with inflammation in the proximal or distal pouch body, sparing other proximal pouch body. The latter pattern is often seen in male patients with excessive weight gain or multiple abdominal or pelvic surgeries, following IPAA. Another pattern of ischemic pouchitis is the presence of linear ulcers along the vertical staple line in the pouch body or circumferential ulcers at the LI site, inlet or at the anastomosis. The contribution of technical or anatomic factors, such as ischemia, to the development of pouchitis is testified by the fact that patients with the J-pouch have a high risk for the development of chronic pouchitis than those with the S- or K-pouches, due to mainly the “mesenteric” stretch [19, 20]. In our clinical practice at the Center for Ileal Pouch Disorders at Cleveland Clinic, we routinely perform the pouchoscopy to monitor disease activity and evaluate the treatment response, along with diagnosis and surveillance. For patients without symptoms, we even recommend them to have diagnostic pouchoscopy every 1 or 2 years, in corporation with surveillance pouchoscopy. The diagnostic and/or surveillance pouchoscopy in asymptomatic patients with IPAA often showed structural or inflammatory disease conditions [21]. Of 138 asymptomatic patients from our Center for Ileal Pouch Disorders, 69 (50%) had abnormal endoscopic findings, 102 (73.9%) had acute and/or chronic inflammation on histology, and 62 (44.9%) had both abnormal endoscopy and histology. The abnormal endoscopic findings included pouch ulcers (N=29, 21%), active pouchitis (N=31, 22.5%), inflammatory polyps (N=10, 7.2%), strictures at the anastomosis (N=5, 3.6%), inlet (N=10, 7.2%), or outlet (N=2, 1.4%) [17]. Chronic, smoldering inflammation in patients with minimum or no symptoms can result in stiffness of the pouch, if left untreated. One of endoscopic features which should be closely monitored is the extensibility or stiffness of the pouch (Fig. 15.5B) and loss of the “owl’s eye” configuration (Figs. 15.6 and 15.8). The use of histology in the diagnosis and differential diagnosis for the pouch disorders is discussed in Chapter 16. Like the situation in CD or UC, the degree of inflammation on histology is not correlated with that measured on endoscopy [3, 22, 23]. Endoscopic evaluation is more reliable to quantify the degree of pouch inflammation than histology [23]. In fact, for the diagnosis of pouchitis, the histology subscore may be omitted without sacrifice of diagnostic accuracy of the PDAI, leading to these authors’ proposed modified PDAI (mPADI) score [12]. Due to its convenience and avoidance of a delayed diagnosis, mPDAI has increasingly been used for the diagnosis and monitoring of pouchitis [24], and in clinical trials [25, 26]. Histologic score alone is seldom used in the diagnosis of pouchitis or in grading of inflammation, in our clinical practice. However, histologic and immunohistochemical features may provide clues for the diagnosis and differential diagnosis of pouchitis, such as intramucosal fibrosis for prolapse, non-mucinous, noncaseating granulomas for CD of the pouch, increased number of crypt apoptosis in AImD-associated pouchitis [27], intramucosal hemorrhage, dropout of crypts and extracellular deposition of hematoidin for ischemic pouchitis [12], and giant histiocytes with inclusion bodies in CMV infection. Therefore, a combined assessment of symptomatology, endoscopy, and histology is often needed for the diagnosis of pouchitis and other pouch disorders. Immunohistochemistry may show excessive number of IgG4-expressing plasma cells in the lamina propria in patients with IgG4-associated pouchitis [28] and even mastocytosis [29].

CD of the Pouch The ileal pouch surgery is generally indicated only for patients with underlying UC or indeterminate colitis, and seldom for those with Crohn’s colitis. However, a subset of patients with UC or indeterminate colitis may develop de novo CD of the pouch with an estimated frequency ranging from 3% to 13% [30–38]. Endoscopic features of CD of the pouch included ulcers and strictures at the afferent limb or pouch inlet, pouch body, late-onset (i.e., more than 6–12 months after ileostomy closure) perianal fistula or PVF. While the presence of non-mucinous, noncaseating granulomas on mucosal biopsy of the afferent limb, pouch body, or cuff suggests the diagnosis of CD of the pouch, none of the endoscopic features is diagnostic for CD of the pouch. CD of the pouch can be classified into: (1) inflammatory; (2) fibrostenotic; and (3) fistula phenotypes.

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Of note, the long-term NSAID use can cause inflammation or stricture in any parts of GI tract in pouch patients. Surgeryassociated ischemia can also cause inflammation, stricture, or fistula. Iatrogenic injury can cause anastomotic fistula, the tip of “J” leak and PVF. Those surgery-associated lesions can completely overlap with that seen in CD on endoscopy. It has been hard to distinguish CD of the pouch from NSAID- or ischemia/surgery-associated inflammation, strictures, or fistula. Following endoscopic features may provide clues for CD, rather than ischemia or surgery-associated complication: (1) recurrent stricture, sinus, or fistula which were treated with endoscopy; (2) strictures outside the anastomosis, pouch inlet, and LI site; (3) fistula orifice outside of the anastomosis, tip of the “J”, or base of the nipple valve in the Kock pouch; (4) concurrent inflamed mucosa around the orifice of fistula; (5) the presence of complex or branched perianal fistula; (6) the presence of upper GI tract lesions; and (7) favorable response to anti-tumor necrosis factor (TNF), anti-integrin, or anti-interleukin (IL) 12/23 therapy.

Cuffitis The anatomic term of cuff in the literature has been confusing. The terminology of cuff can be macroscopic or microscopic. Macroscopically, the cuff is the distal segment of the rectum between the anatomic anal canal and the surgical anal canal; and microscopically, the cuff is characterized by the presence rectal columnar mucosa, different from villous mucosa of the pouch, and squamous epithelia in the ATZ or anatomic anal canal. Cuffitis, an inflammatory disorder of the residual rectal mucosa in pouch patients with non-mucosectomy stapled anastomosis. Classic cuffitis is traditionally considered as a reminiscent form of UC, with the unique presentation of bleeding, which is often absent in pouchitis or CD of the pouch [14, 39]. Classic cuffitis typically present with circumferential diffuse inflammation with or without ulceration, limited to the cuff. In fact, cuffitis patients within an excessively long cuff, due to technical difficulty during pouch construction, may resemble the classic picture of UC proctitis. Occasionally, cuffitis can be seen in patients with mucosectomy, due remnant rectal mucosa. Cuffitis may also result from other factors such as ischemia [40], trauma, and prolapse, which can be demonstrated with careful endoscopic examination. Ischemic cuffitis may show asymmetric discrete inflammation and/ or ulceration and prolapse-associated cuffitis may have concurrent distal pouch and/or cuff prolapse at the anterior wall. Therefore, not all patients with cuffitis respond favorably to topical mesalamine or corticosteroid therapy [41]. Cuffitis can also be part of IMP or CD of the pouch. Therefore, the evaluation of cuffitis should be put into context of the whole ileal pouch picture. The diagnosis and management of cuffitis is detailed in Chapter 25.

Structural Disorders of the Pouch Patients with structural disorders of pouch present with various symptoms which may overlap with that in pouchitis. Those structural disorders were listed in The Cleveland Clinic Classification of Ileal Pouch Disorders [42, 43] (Chapter 8). Pouchoscopy is a main tool to distinguish pouchitis from those disorders. In clinical practice at our Pouch Center, pouchoscopy has been used as a “triage” tool for in-depth evaluation. The majority of surgery-associated structural complications can be detected by careful endoscopic examination. Those include stricture, anastomotic sinus, the leak at the tip of the “J”, prolapse, twisted or folded pouch, angulation of pouch inlet (i.e., afferent limb syndrome or ALS), angulation at excessively long efferent limb in an S-pouch, or excessively long rectal cuff in a J-pouch (i.e., ELS). In patients with ALS, endoscopist may find it difficult to intubate the pouch inlet, due to a sharp angulation or prolapse. Special endoscopic tools may be needed to further delineate the structural disorders, such as guide wires for the sinus, fistula, or the leak of the tip of “J”, and betadine hydrogen peroxide spray for fistula. For complex structural disorders of the pouch, abdominal imaging, such as contrasted pouchogram, defecography, computed tomography (CT), magnetic resonance imaging (MRI) enterography, or MRI of the pelvis may be needed. In addition, examination under anesthesia in the operative room with a team of IBD specialist and colorectal surgeon may also be required [44].

Functional Disorders of the Pouch The typical example of functional disorders of the pouch is IPS. The symptomatology of IPS almost completely overlap with that in pouchitis and other inflammatory disorders of the pouch. Currently, IPS is the diagnosis of exclusion, that is, the exclusion of structural or inflammatory conditions of the pouch and celiac disease. By definition, patients with IPS should have no endoscopic inflammation and no or minimum histologic inflammation. On pouchoscopy, patients with IPS may demonstrate hyperperistalsis and excessive mucus. Mucosal biopsy may show enterochromaffin cell hyperplasia [45].

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Patients with paradoxical contractions often present with dyschezia and occasionally bleeding. Excessive straining may cause prolapse and inflammation of the anterior distal pouch or cuff. Patients with a mega pouch may have diffuse mild mucosal inflammation in the dilated pouch body, due to the long-term fecal stasis.

ENDOSCOPY IN SURVEILLANCE OF POUCH NEOPLASIA Proctocolectomy significantly reduces the risk for colitis-associated neoplasia (CAN). However, the risk for neoplasia is not completely abolished in patients with ileal pouches, even in patients with mucosectomy [46, 47]. Almost all reported cases of adenocarcinoma or squamous cell cancer in the pouch is the location of cuff or ATZ. Two large studies, one from Cleveland Clinic and other from Netherlands, demonstrated that a preoperative diagnosis of CAN increased the risk for the development of pouch neoplasia [33, 34]. Therefore, the annual surveillance pouchoscopy with biopsy is recommended for patients with a preoperative diagnosis of CAN or familial adenomatous polyposis (FAP). It may be prudent to perform annual surveillance pouchoscopy in patients with purported risk factors for pouch neoplasia, such as long disease duration of UC, family history of colon cancer, and the presence of PSC or chronic pouchitis or chronic cuffitis (Chapter 24). Careful examination, even with image-enhanced endoscopy (such as chromoendoscopy [48], andconfocal laser endomicroscopy [49], and narrow band imaging) biopsy of the cuff or ATZ is critical for effective surveillance biopsy. Extensive and deep biopsy of the cuff or ATZ is advocated in pouch patients with a preoperative diagnosis of CAN or with FAP. Annual surveillance pouchoscopy along with esophagogastroduodenoscopy (EGD) should also be performed in pouch patients with underlying PSC for the purpose of evaluation of esophageal and gastric varices and IMP. For FAP patients with heavy burden of tumor, periodic surveillance with VCE is advocated.

EGD AND CAPSULE ENDOSCOPY Patients with UC or ileal pouches are not immune to disease in the upper and mid-GI tract. We have advocated that each UC patient before restorative proctocolectomy should have an evaluation of upper GI tract with EGD for the identification of diseases like CD, celiac disease, eosinophilic esophagitis/gastritis/duodenitis. The role of routine preoperative video capsule endoscopy (VCE) for the screening small bowel CD in patient having pouch surgery is not well established. The investigators from Cedars Sinai Medical Center, Los Angeles performed VCE in 68 patients with UC or indeterminate colitis undergoing IPAA and found abnormal VCE in 15 patients (22%). The postoperative frequencies of acute pouchitis, chronic pouchitis, de novo CD of the pouch, and pouch inflammation were comparable between the abnormal VCE and normal VCE groups [50]. Therefore, routine precolectomy VCE may not predict the occurrence or course of pouchitis or other pouch disorders. In patients with “upper GI clearance” by EGD or VCE can still develop various diseases after pouch construction. After pouch construction, EGD with biopsy has been used as an adjunct modality for the diagnosis and differential diagnosis and prognosis of various pouch disorders. We studied 66 patients with patients with EGD of whom 64 (97%) patients had a concomitant pouch endoscopy. Indications for EGD included anemia, upper abdominal pain, weight loss, nausea and vomiting, and persistent diarrhea refractory to antibiotic therapy were evaluated. We found that 17 patients (25.8%) had a conclusive diagnosis and 14 (21.2%) had incidental findings, based on EGD. The most common abnormal findings on EGD were CD (12%), peptic ulcer disease (3%), gastritis/duodenitis on histology (11%), Candida esophagitis (3%), and arteriovenous malformations (3%) [51]. Our group further studied 96 patients who had both EGD and pouchoscopy and found that acute inflammation in the duodenum as measured by neutrophil infiltration score and the presence of chronic pouchitis [52]. EGD is also performed for the evaluation and treatment of esophageal and/or gastric varices in patients with concurrent PSC or those with porto-mesenteric vein thrombosis from the abdominal/pelvic surgery. EGD evaluation can provide clues for the diagnosis of CD of the pouch or IMP (such as PSC-associated pouchitis and IgG4-associated pouchitis), as the duodenum in those disorders can be involved [author’s unpublished data]. EGD with biopsy is critical for the diagnosis of celiac disease, as de novo celiac disease can occur in patients with pouch surgery [53, 54]. The fact that de novo CD and de novo celiac disease can occur after ileal pouch surgery has prompted our theory of changing “immune thermostat” by the surgery. Iron deficiency anemia (IDA) and anemia of chronic disease (ACD) are common in patients with the ileal pouch or IBD in general. Anemia from acute and/or chronic bleeding through the GI tract is not common. Therefore, EGD and VCE evaluation in patients with chronic anemia often lead to a negative finding. Our group studied 17 pouch patients with anemia (hemoglobin <10 g/dL). VCE was successfully completed in 16 patients (94.1%). Suspected causes of anemia were identified in 5 patients (29.4%): two patients with CD of the pouch, one with CD of small bowel, one with celiac disease, detected by EGD and pouchoscopy with biopsy along with celiac disease serology, and one small bowel arteriovenous

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FIG. 15.15  Special endoscopies. (A) Capsule endoscopy for the evaluation anemia in pouch patients; (B) endoscopic retrieval of retained capsule in a Kock pouch; (C and D) endoanal ultrasound detection of a perianal abscess (yellow arrow).

malformations [55]. The findings suggest that VCE in patients is feasible and may be valuable in the evaluation of anemia (Fig. 15.15A and B). It is not clear whether VCE is safe in patients with known CD, for the concern of capsule retention. Patients with a Kock pouch who undergo VCE should be prepared for subsequent pouchoscopy to retrieve the capsule.

OTHER ENDOSCOPY MODALITIES A variety of conditions of the pouch may require the assessment of special endoscopies.

Ileoscopy via Stoma Ileostomy is constructed for the staged pouch surgery or for the treatment of severe refractory pouch disorders. Either end ileostomy or LI is created, for a temporary or permanent purpose. The assessment of inflammation in the small bowel segment proximal to the stoma is important for the decision of stoma closure and diagnosis and management of disease conditions there. The ileoscopy can be performed with the use of an EGD. During ileoscopy via stoma, peristomal skin, stoma, and small bowel segment should be carefully examined for peristomal ulcer, parastomal pyoderma gangrenosum, stoma ulcer, stoma retraction or prolapse, and inflammation, stricture, and fistula in the small bowel. Diffuse enteritis on ileoscopy after colectomy raises the suspicion for the diagnosis of post-colectomy enteritis syndrome [56]. CD can occur in patients with temporary or permanent ileostomy, especially in those with secondary ileostomy due to failed ileal pouches [57].

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CD in the neo-distal small bowel in patients with ileostomy typically results in an aggressive disease course, which requires adequate medical, endoscopic or surgical therapy and close monitoring. Special attention should be paid to the area of insertion of abdominal fascia, typically 5–15 cm from stoma, depending on the patient’s weight and thickness of abdominal wall. The area is prone to the development of ulcers, stricture, and fistula, which do not necessarily indicate CD (see details in Chapter 5).

Small Bowel Endoscopy Push enteroscopy or balloon-assisted enteroscopy is hardly used in patients with ileal pouches. This author has used enteroscopy for the treatment of strictures deep in the small bowel with balloon dilation or endoscopic stricturotomy. Extreme caution should be taken due to the concern of a higher risk for procedure-associated perforation.

Optical Coherence Tomography Optical coherence tomography (OCT), with its imaging penetration of 1–2 mm may provide information of deeper layers of bowel wall. Our group evaluated ex vivo and in vivo OCT and found that a disrupted layer pattern may help differential diagnosis of CD vs. UC [58, 59]. However, layered bowel structure is disrupted in both chronic pouchitis and CD of the pouch [60]. Clinical implications of this feature on OCT warrants further investigation.

Endoscopy Ultrasonography Endoscopic ultrasonography (EUS) has been used to guide medical therapy in CD patients with perianal fistula and abscess [61]. EUS has also been performed for the drainage of pelvic abscess in patient with IPAA [62]. Endoanal sonography has been used to assess the anal sphincter anatomy in patients with IPAA [63]. We occasionally use endoanal sonography to evaluate perianal fistula (Fig. 15.15C and D).

Intraoperative Endoscopy Pouchoscopy or ileoscopy via stoma is occasionally performed by endoscopy team and/or surgical team, in operative room as a part of examination under anesthesia. The author’s team have performed a combined pouchoscopy and laparoscopy procedure in the treatment of patients with multiple strictures in the afferent limb and pouch inlet.

SUMMARY AND RECOMMENDATIONS Pouchoscopy plays the key role in the initial evaluation of patients with symptoms of pouch dysfunction, to assess for the presence of pouchitis or other structural, inflammatory, and functional disorders. Pouchoscopy is more reliable to quantify the degree of inflammation than histology, although they complement each other. Pouchoscopy is also important for the monitoring of disease activity and assessment of treatment response and for dysplasia surveillance. During the surveillance pouchoscopy, careful evaluation and biopsy of the cuff or ATZ is the key. In selected patients with ileal pouches, EGD and VCE are needed.

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