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Adverse Metabolic Conditions after Pouch Surgery
Chapter 13
Adverse Metabolic Conditions after Pouch Surgery Bo Shen, MD Center for Inflammatory Bowel Diseases, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, United States
ABBREVIATIONS BMD bone mineral density CA cholic acid CDCA chenodeoxycholic acid CI confidence interval CD Crohn’s disease FAP familial adenomatous polyposis GI gastrointestinal IBD inflammatory bowel disease IDA iron deficiency anemia IPAA ileal pouch-anal anastomosis OR odds ratio PSC primary sclerosing cholangitis QOL quality of life SIBO small intestinal bacterial overgrowth VDR vitamin D receptor UC ulcerative colitis
INTRODUCTION Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for medically refractory ulcerative colitis (UC) or colitis-associated neoplasia [1,2]. The exact same procedure is also performed in patients with familial adenomatous polyposis (FAP). IPAA offers the advantage of avoiding a permanent ostomy by creating a continent fecal reservoir and maintaining bowel continuity. In contrast to various “destructive” surgeries, such as cholecystectomy, appendectomy, and hysterectomy, this “reconstructive” surgery is not so “natural”. Therefore, a variety of inflammatory and noninflammatory complications emerge following IPAA and those include pouchitis, cuffitis, de novo Crohn’s disease (CD) of the pouch, anastomotic leak, sepsis, abscess, and sinus. In addition, systemic and metabolic consequences in patients with healthy or diseased pouches have increasingly been recognized [1]. In this chapter, the author summarizes common metabolic complications after ileal pouch surgery, including anemia, iron deficiency, vitamin B12 deficiency, vitamin D deficiency, bile salt malabsorption, bone loss, nephrolithiasis, and metabolic syndrome.
ANEMIA AND IRON DEFICIENCY Anemia is common in patients with ileal pouches, with a reported frequency of 17%–21% [3,4]. Iron deficiency can be seen in up to 56% (10 of 18 patients) of selected patient populations with pouches [5]. The etiology and pathogenesis of anemia in pouch patients are not clear. It is likely multifactorial. In this population, normocytic anemia occurred in 74% of patients, microcytic anemia in 24%, and macrocytic anemia in 2% [4]. Reported Pouchitis and Ileal Pouch Disorders. https://doi.org/10.1016/B978-0-12-809402-0.00013-7 © 2019 Elsevier Inc. All rights reserved.
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risk factors for anemia in patients with IPAA for underlying UC or FAP included the presence of J-pouch (vs. S- or Kock pouches) [4], or concurrent pouchitis, concurrent malignancy and desmoid tumors [3,5], Finally, anemia of chronic disease, which occurs in patients with chronic mucosal inflammation or small bowel intestinal bacterial overgrowth (SIBO) [6], may contribute to anemia seen in pouch patients. This author also noticed that patients with a large-volumed J-pouch and dilated afferent limb often have anemia. Iron deficiency is common in pouch patients in the presence or absence of anemia [5]. Postulated mechanisms of iron deficiency include poor oral intake, decreased absorption and utilization, intermittent blood loss, and increased requirements [7]. Similar to iron deficiency in non-pouch patients with inflammatory bowel disease (IBD), those with pouches have a poor tolerance of oral iron supplement, suggesting a major role played by the poor iron absorption and/or utilization, that is, iron deficiency/anemia of chronic diseases, in those patients. Attempts have been made to establish a connection between chronic blood loss and anemia. Unlike iron deficiency anemia (IDA) from chronic gastrointestinal (GI) bleeding in which patients normally tolerate oral iron supplement, pouch patients with anemia often have dyspepsia while taking oral iron. Although we occasionally see patients with slow, intermittent bleeding from cuffitis, suture line or anastomotic ulcers, or inflammatory polyps, we often are not able to identify bleeding lesions in the GI tract in the majority of patients with IDA. In fact, the author’s group has investigated the etiology of IDA in pouch patients, with an extensive work-up consisting of esophagogastroduodenoscopy, pouchoscopy, small bowel histology, capsule endoscopy, and celiac serology. We found definitive or possible etiology of IDA in only 29% of patients with ileal pouches [8]. These findings suggest that chronic GI bleeding is not a main etiology. De novo celiac disease following restorative proctocolectomy with IPAA has been described in case reports [9,10]. Since the establishment of the Center for Ileal Pouch Disorders at Cleveland Clinic in 2002, the author’s group have encountered 20 patients with de novo celiac disease. It is not clear whether the pouch surgery triggers the development of de novo celiac disease. It is interesting that a majority of those patients did not respond to gluten-free diet and required corticosteroid and/or immunomodulator therapy. Nevertheless in pouch patients with anemia and/or GI symptoms, we routinely screen for celiac disease.
VITAMIN B12 DEFICIENCY Vitamin B12 or cobalamin is a water-soluble vitamin which plays a key role in neural system as well as in the formation of blood. The physiology and pathophysiology of vitamin B12 absorption is complex. Vitamin B12 is released from dietary sources by acid and pepsin. R factor released from the saliva gland binds to free vitamin B12 protects it from degradation. In the duodenum, R factor is cleaved by proteases, allowing for vitamin B12 to bind to intrinsic factor produced by the stomach. The B12-intrinsic factor complex moves downward to the distal ileum where it is absorbed by ileal intrinsic factor receptors. Luminal bacteria can bind vitamin B12 and utilize it for in their metabolic activities, which can interfere with its normal transluminal uptake. It has been anticipated that patients with ileal pouches are at a high risk for vitamin B12 deficiency, as the pouch body created from the distal ileum inherently has fecal stasis, adaptive mucosal changes (colonic metaplasia), SIBO with subsequent microbial binding, and utilization of luminal vitamin B12, poor oral intake, and dietary restrictions. In a study of 171 with restorative proctocolectomy and IPAA, 25% of IPAA patients were found to have vitamin B12 deficiency but with normal Shilling’s tests [11]. Vitamin B12 deficiency in pouch patient can be corrected with oral supplementation, suggesting the role of poor intake in its development [11]. It appears that bile acids play a role in B12 absorption too. A separate study showed that 56% of pouch patients with vitamin B12 deficiency had bile salt deconjugation as measured by 14 C-glycocholic acid breath test and fecal bile acid level [12]. Those findings suggest that bacterial overgrowth or overload may be contributing factor [12]. While a large quantity of bacteria can bind vitamin B12 and prevent the latter from being absorbed, bacteria can also produce vitamin B12. It is not clear whether a long-term antibiotic or probiotic use in pouch patients has a positive or negative impact on B12 absorption. Small intestinal bacterial overgrowth is a norm in patients with ileal pouches. Contributing factors are anatomic and/or motility changes. The loss of the ileocecal valve during colectomy and ileal pouch construction leads to the reflux of pouch content to the proximal segment of small bowel. The current clinical standard practice in diagnosis of SIBO is glucose or lactulose breath tests and their use in the setting of the ileal pouch is controversial, as the breath tests standardized in patients with an intact colon. It is interesting that SIBO diagnosed by breath test was not reported to be associated with chronic pouchitis [13]. Whether the pouch surgery per se has an impact on vitamin B12 metabolism is not clear. In a cross-sectional study, vitamin B12 deficiency was found in 13% of UC patients before colectomy, and only 3% of patients with IPAA [14]. Possible explanations may be improved general nutritional status of the patients and increased bacterial production of vitamin B12
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in the pouch reservoir. Although villous atrophy or colonic metaplasia of the ileal pouch mucosa is common in patients with healthy or inflamed pouch [15,16]. Clinically significant vitamin B12 deficiency in pouch patients appears to be rare. The exceptions include strict vegetarians, concurrent gastric bypass surgery, and pernicious anemia.
BILE ACID MALABSORPTION Bile acids play a key role in fat and fat soluble vitamin absorption. Primary bile acids are produced in the liver and excreted in bile and secondary bile acids are formed from bacterial actions in the colon. They are preferentially (95%) absorbed in the terminal ileum through enterohepatic circulation. Bile acid malabsorption or bile acid diarrhea occurs when reabsorption is impaired due to ileal disease or ileal resection and bile acidss stimulate water secretion and intestinal motility. Bile acid metabolism and its impact on mucosal inflammation in patients with ileal pouches have been investigated. Aqueous phase fecal bile acids have been measured in patients following IPAA [17]. An alteration in the luminal bile acid pool may be involved in pouch inflammation [18]. In patients with IPAA, pool sizes of cholic acid (CA) and chenodeoxycholic acid (CDCA) were significantly lower than in healthy controls. In addition, fractional turnover rates of CA and CDCA were higher in those with IPAA than healthy controls. It is speculated that a reduced pool size of primary bile acids may contribute to the high frequency of cholesterol gallstones in patients with proctocolectomy and IPAA [19]. The change in bile acid pool in patients with IPAA is also evidenced by the investigation of patients with primary sclerosing cholangitis (PSC). PSC patients have known abnormalities in biliary structure and bile metabolism and flow. Biliary enrichment of ursodeoxycholic acid in pouch patients with PSC may be reduced [20]. Our group reported that pouch patients with PSC have a greater degree of endoscopic and histologic inflammation in the pouch body or distal afferent limb than pouch patients without PSC [21]. Clinically, almost all pouch patients with concurrent PSC have some degree of inflammation in the pouch and afferent limb and interestingly, their symptoms of diarrhea and abdominal cramps are often mild. This phenotype of disease has been labeled as “PSC-associated pouchitis/enteritis”, a part of immune-mediated pouchitis [22]. Inflammatory changes in the pouch are postulated to manifest as changes in bile acid conjugation and dehydroxylation [19],rather than changes in bile acid composition [23]. Villous atrophy, colonic metaplasia, and chronic pouchitis may result from or result in decreased bile salt absorption [24,25]. Diseased ileum or pouch mucosa can impair bile acid and fat absorption, as evidenced by a study showing abnormal 75selenium homotaurocholate uptake test in 7 of 8 pouch patients, and by analysis of abnormal 14C triolein breath test in 3 of 8 pouch patients [26].
VITAMIN D DEFICIENCY Vitamin D, a fat soluble vitamin is primarily absorbed in the duodenum and jejunum. It is hydroxylated in the liver to form 25-OH vitamin D and in the kidney to form 1, 25-OH vitamin D. It appears that the association between vitamin D metabolism and IBD is reciprocal. Chronic gut inflammation may interfere with vitamin D metabolism and deficiency in vitamin D, an “anti-inflammatory” substance, may increase the risk for the development of inflammation. Vitamin D receptor (VDR) is an important component in maintaining mucosal integrity [27,28], and its abnormality has been implicated in the pathogenesis from dextran sulfate sodium. In contrast, VDR knockout mice were prone to develop severe colitis [25]. In other murine models, inflammation of the GI tract develops in VDR knockout animals [26]. In a study of 188 patients with pediatric-onset UC of whom 33 (18%) underwent restorative proctocolectomy and IPAA, the investigators reported that preoperative vitamin D deficiency (≤20 ng/mL) was associated with an increased hazard ratio of 4.4 for the risk of pouchitis [29]. Clinically, vitamin D deficiency is common in patients with IBD [30],with the lowest level seen in those with severe disease [31,32]. IBD patients with vitamin D deficiency had quality of life (QOL), independently from the disease activity [29]. In an earlier study of 107 patients with ileal pouches, the frequency of vitamin D deficiency was reported in 11% of patients [15]. In contrast, a cohort study of 157 patients from the Cleveland Clinic showed that the frequency of vitamin D deficiency was 69% [33]. Similarly, a recent letter to the editor reported vitamin D deficiency in 80% of patients with IPAA [34]. Interestingly, anemia was found to be an independent risk factor for vitamin D deficiency. The geographic location of patients, season of measurement, and medications were not found to be associated with vitamin D deficiency in those patients [30]. In addition, there was no significant association found between pouch inflammation and vitamin D deficiency [30]. The presence of concurrent PSC, however, in pouch patients posed a risk for vitamin D deficiency [35]. It is not clear whether the commonly encountered low vitamin D level has any adverse impact on the pouch outcomes. However, we speculate that low vitamin D at least can affect the bone metabolism in pouch patients.
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BONE LOSS AND BONE FRACTURE Bone loss is common in patients with IBD and patients with IPAA are not an exception. In a study of 53 patients from St Mark’s Hospital, London, the frequency of osteopenia and osteoporosis was reported to be 43% and 13%, respectively [36]. In a separate study of 327 pouch patients from the Cleveland Clinic, 105 patients (32%) had low bone mineral density (BMD) with either osteoporosis or osteopenia [37]. The reported incidence of fragility fractures ranged from 7% to 15% [34,38]. Factors associated with a low BMD were found to be advanced age, low body mass index, and no calcium supplementation. Interestingly, factors related to the pouch condition itself, such as the presence of chronic pouchitis and CD of the pouch were not found to be associated with the bone loss [34]. The construction of an ileal pouch, with or without inflammatory conditions of the reservoir may or may not have a beneficial or detrimental impact on bone metabolism. It is known that patients with UC are at risk for bone loss [39]. However, there are conflicting reports on the impact of colectomy and IPAA on BMD. In a study of 267 patients with UC and IPAA and 119 patients with UC without IPAA, 83 (31.1%) and 18 (15.1%) had a low BMD, respectively. Interestingly, 64 UC patients with IPAA (24.0%) were on corticosteroid therapy postoperatively, as compared to 93 (78.2%) in the nonpouch UC patients. The presence of IPAA per se (odds ratio [OR]:6.02; 95% confidence interval [CI], 2.46–14.70) was an independent risk factor for low BMD [40]. A separate longitudinal study showed that BMD values increased over time after IPAA surgery [39]. The etiology and pathogenesis of bone loss in IPAA patients are multifactorial. In addition to the reported risk factors such as advanced age, a low body mass index [16,34,37], and lack of calcium supplementation [34], vitamin D and parathyroid hormone should play a role. The adaptive change of the small bowel and pouch mucosa from fecal stasis in pouch patient may also be a contributing factor. In fact, 37% of IPAA patients with villous atrophy had osteopenia, compared to 0% with normal villous structure [16]. The lowest BMD scores were found in patients with inflammation in the afferent limb [16]. The presence of inflammation is associated with circulating cytokines such as interleukins (IL-1 and IL-6) and tumor necrosis factor-α, which stimulate osteoclast activity and lead to bone reabsorption and bone loss [41]. Supplementation of calcium and vitamin D has been shown to increase BMD scores in patients with IBD [42]. Although an increased inflammatory activity of the pouch has been associated with a lower BMD, the clear connection between pouchitis and vitamin D deficiency remains to be determined. There are no published on improvement of BMD by anti-inflammatory therapy in pouch patients. Of interest, the frequent bone loss does not translate an increased risk for bone fracture. In fact, fracture risk after IPAA was shown to be reduced as compared with UC patients without IPAA. In a study of 1757 IPAA patients, as compared with 8785 UC controls, from a national cohort of Danish UC patients, the adjusted hazard ratio of fracture was 0.49 (95% CI: 0.43; 0.55) [43].
NEPHROLITHIASIS Overall QOL is often improved following IPAA [44,45], symptomatic nephrolithiasis after the surgery can compromise the gain in QOL. The prevalence of nephrolithiasis has been estimated at 5% of the general population [46], and 7% in patients with IBD [47]. The purported risk factors associated with nephrolithiasis in IBD patients have been postulated including diarrhea, dehydration, and low urine volume, pH, citrate, and magnesium, and elevated urine oxalate [48]. The author’s group reported that 37% of patients with IPAA in the Center for Ileal Pouch Disorders at the Cleveland Clinic had nephrolithiasis. The majority of these patients had symptomatic stones. The presence of extraintestinal manifestations, non-use of antibiotics, and lower serum bicarbonate levels were found to be risk factors for developing kidney stones [44]. Our group prospectively studied 40 patients with or without nephrolithiasis. There were no significant differences in serum electrolytes, vitamin D, parathyroid hormone, and kidney function tests between the study (n=20) and control (n=20) groups. Patients in the nephrolithiasis group were found to have a higher 24-h urine supersaturation of calcium oxalate and calcium phosphate than controls. Nineteen (95%) patients in the study group were symptomatic due to nephrolithiasis with several requiring procedural intervention for treatment, including ureteroscopy in three (15%) patients, lithotripsy in five (25%), and percutaneous surgery in one (5%) [49]. Adequate oral hydration is critical for prevention of nephrolithiasis in patients with IBD, ileal pouches, or stomas. The management of nephrolithiasis and bone loss in patients with the ileal pouch can be contradictory, that is, supplement of oral calcium and vitamin D.
FAT METABOLISM It is known that obese patients undergoing restorative proctocolectomy with IPAA pose greater technical challenges for surgeons and have a great risk of postoperative complications [50,51]. Excessive weight gain and fat accumulation may
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also have an adverse impact on the long-term outcome of the pouch. Abnormal fat metabolism in patients after the ileal pouch can be manifested by fat malabsorption and fat gain. Fat malabsorption appeared to be associated with bile acid malabsorption. Fat absorption was reported to be reduced in patients with IPAA as compared to those with ileostomies [52]. In patients with healthy or diseased pouch construction, the presumed fecal stasis with bacterial overload could lead to bile salt deconjugation and a decreased absorption as measured by 75selenium homotaurocholate, as compared to those with healthy pouches [24]. Clinically, decreased serum total low density lipoprotein cholesterol levels, and triglycerides have been reported in patients with IPAA [53]. While patients with surgical procedure-associated, mechanical disorders of the pouch (such as presacral sinus and afferent limb syndrome) or CD of the pouch are often underweight, patients with a healthy pouch often gained weight after the pouch construction from generally improved health and oral intake. However, the author’s group found that an excessive weight gain is associated with a higher risk pouch failure from pouch sinus and chronic pouchitis [54]. It is speculated that central obesity or gain in the mesenteric fat, rather than cutaneous fat, is the main contributing factor [55].
SUMMARY AND RECOMMENDATION Long-term metabolic consequences have increasingly been recognized in patients with ileal pouches. These include anemia, iron deficiency, preexisting, or de novo celiac disease, vitamin B12 deficiency, bile salt malabsorption, vitamin D deficiency, bone, and nephrolithiasis. The etiology and pathogenesis are likely multifactorial. Those adverse metabolic sequelae can occur in patients without pouch inflammation. Clinicians should be aware of these conditions in patients with healthy and diseased pouches, so that appropriate screening and patient counseling may take place.
REFERENCES [1] Shen B, Remzi FH, Lavery IC, Lashner BA, Fazio VW. A proposed classification of ileal pouch disorders and associated complications after restorative proctocolectomy. Clin Gastroenterol Hepatol 2008;6:145–58. [2] Buckman SA, Heise CP. Nutrition considerations surrounding restorative proctocolectomy. Nutr Clin Pract 2010;25:250–6. [3] Tiainen J, Matikainen M. Long-term clinical outcome and anemia after restorative proctocolectomy for ulcerative colitis. Scand J Gastroenterol 2000;35:1170–3. [4] Oikonomou IK, Fazio VW, Remzi FH, Lopez R, Lashner BA, Shen B. Risk factors for anemia in patients with ileal pouch–anal anastomosis. Dis Colon Rectum 2007;50:69–74. [5] Pastrana RJ, Torres EA, Arroyo JM, Rivera CE, Sánchez CJ, Morales L. Iron-deficiency anemia as presentation of pouchitis. J Clin Gastroenterol 2007;41:41–4. [6] Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011–23. [7] M’Koma AE, Wise PE, Schwartz DA, Muldoon RL, Herline AJ. Prevalence and outcome of anemia after restorative proctocolectomy: a clinical literature review. Dis Colon Rectum 2009;52:726–39. [8] Shen B, Remzi FH, Santisi J, Lashner BA, Brzezinski A, Fazio VW. Application of wireless capsule endoscopy for the evaluation of iron anemia in patients with ileal pouches. J Clin Gastroenterol 2008;42:897–902. [9] Shen L, Lian L, Goldblum JR, Remzi FH. Development of de novo celiac disease after restorative proctocolectomy and ileal pouch–anal anastomosis. Inflamm Bowel Dis 2009;15:1131–2. [10] Tyler AD, Murdoch TB, Riddell RH, Silverberg MS. Celiac disease detected by pouch biopsy of a patient with ileal pouch-anal anastomosis. Am J Gastroenterol 2011;106:1367–8. [11] Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Color Dis 2007;9:562–6. [12] Hylander E, Rannerm T, Hegnhøj J, Kirkegarrd P, Thale M, Jarnum S. Absorption studies after ileal J-pouch anastomosis for ulcerative colitis: a prospective study. Scand J Gastroenterol 1991;26:65–72. [13] Lisowska A, Banasiewicz T, Marciniak R, et al. Chronic pouchitis is not related to small intestine bacterial overgrowth. Inflamm Bowel Dis 2008;14:1102–4. [14] M’Koma AE. Follow-up results of hematology data before and after restorative proctocolectomy: clinical outcome. Dis Colon Rectum 1994;37:932–7. [15] Kuisma J, Nuutinen H, Luukkonen P, Järvinen H, Kahri A, Färkkilä M. Long term metabolic consequences of ileal pouch–anal anastomosis for ulcerative colitis. Am J Gastroenterol 2001;96:3110–6. [16] Kuisma J, Luukkonen P, Järvinen H, Kahri A, Färkkilä M. Risk of osteopenia after proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis. Scand J Gastroenterol 2002;37:171–6. [17] Sandborn WJ, Tremaine WJ, Batts KP, et al. Fecal bile acids, short-chain fatty acids, and bacteria after ileal pouch-anal anastomosis do not differ in patients with pouchitis. Dig Dis Sci 1995;40:1474–83. [18] Hill MJ, Owen RW. Fecal bile acids in pouch and pouchitis patients: pouchitis workshop. Int J Color Dis 1989;4:221–2. [19] Gotthardt DN, Sauer P, Schaible A, Stern J, Stiehl A, Beuers U. Kinetics of primary bile acids in patients after proctocolectomy and ileal pouch-anal anastomosis. Digestion 2014;90:27–32.
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[20] Rost D, Rudolph G, Kloeters-Plachky P, Stiehl A. Effect of colitis and ileoanal pouch on biliary enrichment of ursodeoxycholic acid in primary sclerosing cholangitis. Dig Dis Sci 2006;51:618–22. [21] Shen B, Bennett AE, Navaneethan U, et al. Primary sclerosing cholangitis is associated with endoscopic and histologic inflammation of the distal afferent limb in patients with ileal pouch-anal Anastomosis. Inflamm Bowel Dis 2011;17:1890–900. [22] Shen B. Pouchitis: what every gastroenterologist needs to know. Clin Gastroenterol Hepatol 2013;11:1538–49. [23] Becker JM, Man CH, Hocking J. Fecal bile acid composition with patients with pouchitis following colectomy and ileal pouch-anal anastomosis. Gastroenterology 1994;106:A650. [24] Nicholls RJ, Belliveau P, Neill M, Wilks M, Tabaqchali S. Restorative proctocolectomy with ileal reservoir: a patholophysiological assessment. Gut 1981;22:462–8. [25] Christl SU, Scheppach W. Metabolic consequences of total colectomy. Scand J Gastroenterol Suppl 1997;222:20–4. [26] Fiorentini MT, Locatelli L, Ceccopieri B, et al. Physiology of ileoanal anastomosis with ileal reservoir for ulcerative colitis and adenomatosis coli. Dis Colon Rectum 1987;30:267–72. [27] Kong J, Zhang Z, Musch MW, et al. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 2008;294:G208–16. [28] Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT. A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol 2003;17:2386–92. [29] Rinawi F, Assa A, Eliakim R, et al. Predictors of pouchitis after ileal pouch-anal anastomosis in pediatric-onset ulcerative colitis. Eur J Gastroenterol Hepatol 2017;29:1079–85. [30] Silvennoinen J. Relationships between vitamin D, parathyroid hormone and bone mineral density in inflammatory bowel disease. J Intern Med 1996;239:131–7. [31] Joseph AJ, George B, Pulimood AB, Seshadri MS, Chacko A. 25 (OH) vitamin D level in Crohn’s disease: association with sun exposure & disease activity. Indian J Med Res 2009;130:133–7. [32] Ulitsky A, Ananthakrishnan AN, Naik A, et al. Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life. JPEN J Parenter Enteral Nutr 2011;35:308–16. [33] Khanna R, Wu X, Shen B. Low levels of vitamin D are common in patients with ileal pouches irrespective of pouch inflammation. J Crohns Colitis 2013;7:525–33. [34] Miller HL, Farraye FA, Coukos J, et al. Vitamin D deficiency and insufficiency are common in ulcerative colitis patients after ileal pouch-anal anastomosis. Inflamm Bowel Dis 2013;19:E25–6. [35] Fialho A, Fialho A, Kochhar G, Shen B. The presence of primary sclerosing cholangitis in patients with ileal pouch anal-anastomosis is associated with an additional risk for vitamin D deficiency. Gastroenterol Rep (Oxf) 2016;4:320–4. [36] McLaughlin SD, Perry-Woodford ZL, Clark SK, et al. Osteoporosis in patients over 50 years of age following restorative proctocolectomy for ulcerative colitis: is DXA screening warranted? Inflamm Bowel Dis 2010;16:250–5. [37] Shen B, Remzi FH, Oikonomou IK, et al. Risk factors for low bone mass in patients with ulcerative colitis following ileal pouch-anal anastomosis. Am J Gastroenterol 2009;104:639–46. [38] Abitbol V, Roux C, Guillemant S, et al. Bone assessment in patients with ileal pouch-anal anastomosis for inflammatory bowel disease. Br J Surg 1997;84:1551–4. [39] Schulte C, Dignass AU, Mann K, Goebell H. Reduced bone mineral density and unbalanced bone metabolism in patients with inflammatory bowel disease. Inflamm Bowel Dis 1998;4:268–75. [40] Navaneethan U, Shen L, Venkatesh PG, et al. Influence of ileal pouch anal anastomosis on bone loss in ulcerative colitis patients. J Crohns Colitis 2011;5:415–22. [41] Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995;332:305–11. [42] Abitbol V, Mary JY, Roux C, et al. Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluoride. Aliment Pharmacol Ther 2002;16:919–27. [43] Christensen AM, Brandsborg S, Vestergaard P, Laurberg S. Comparison of fracture risk between patients with ileal pouch-anal anastomosis for ulcerative colitis and the general population. J Crohns Colitis 2014;8:107–12. [44] Martin A, Dinca M, Leone L, et al. Quality of life after proctocolectomy and ileo-anal anastomosis for severe ulcerative colitis. Am J Gastroenterol 1998;93:166–9. [45] Scarpa M, Angriman I, Ruffolo C, et al. Health-related quality of life after restorative proctocolectomy for ulcerative colitis: long-term results. World Surg 2004;28:124–9. [46] Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC. Time trends in reported prevalence of kidney stones in the United States: 19761994. Kidney Int 2003;63:1817–23. [47] Gelzayd EA, Breuer RI, Kirsner JB. Nephrolithiasis in inflammatory bowel disease. Am J Dig Dis 1968;13:1027–34. [48] Mukewar S, Hall P, Lashner BA, Lopez R, Kiran RP, Shen B. Risk factors for nephrolithiasis patients with Ileal pouches. J Crohns Colitis 2013;7:70–8. [49] Arora Z, Mukewar S, Lopez R, Camino D, Shen B, Hall P. Etiopathogenesis of nephrolithiasis in ulcerative colitis patients with ileal pouch-anal anastomosis. Inflamm Bowel Dis 2017;23:840–6. [50] Klos CL, Safar B, Jamal N, et al. Obesity increases risk for pouch-related complications following restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). J Gastrointest Surg 2014;18:573–9.
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[51] Kiran RP, Remzi FH, Fazio VW, et al. Complications and functional results after ileoanal pouch formation in obese patients. J Gastrointest Surg 2008;12:668–74. [52] Bain IM, Mostafa AB, Harding LK, Neoptolemos JP, Keighley MR. Bile acid absorption from ileoanal pouches using enema scintigraphy. Br J Surg 1995;82:614–7. [53] Hakala K, Vuoristo M, Luukkonen P, Järvinen HJ, Miettinen TA. Impaired absorption of cholesterol and bile acids in patients with an ileoanal anastomosis. Gut 1997;41:771–7. [54] Wu XR, Zhu H, Kiran RP, Remzi FH, Shen B. Excessive weight gain is associated with an increased risk for pouch failure in patients with restorative proctocolectomy. Inflamm Bowel Dis 2013;19:2173–81. [55] Shen B. Problems after restorative proctocolectomy: assessment and therapy. Curr Opin Gastroenterol 2016;32:49–54.
Adverse Metabolic Conditions after Pouch Surgery Bo Shen, MD Center for Inflammatory Bowel Diseases, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, United States
ABBREVIATIONS BMD bone mineral density CA cholic acid CDCA chenodeoxycholic acid CI confidence interval CD Crohn’s disease FAP familial adenomatous polyposis GI gastrointestinal IBD inflammatory bowel disease IDA iron deficiency anemia IPAA ileal pouch-anal anastomosis OR odds ratio PSC primary sclerosing cholangitis QOL quality of life SIBO small intestinal bacterial overgrowth VDR vitamin D receptor UC ulcerative colitis
INTRODUCTION Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for medically refractory ulcerative colitis (UC) or colitis-associated neoplasia [1,2]. The exact same procedure is also performed in patients with familial adenomatous polyposis (FAP). IPAA offers the advantage of avoiding a permanent ostomy by creating a continent fecal reservoir and maintaining bowel continuity. In contrast to various “destructive” surgeries, such as cholecystectomy, appendectomy, and hysterectomy, this “reconstructive” surgery is not so “natural”. Therefore, a variety of inflammatory and noninflammatory complications emerge following IPAA and those include pouchitis, cuffitis, de novo Crohn’s disease (CD) of the pouch, anastomotic leak, sepsis, abscess, and sinus. In addition, systemic and metabolic consequences in patients with healthy or diseased pouches have increasingly been recognized [1]. In this chapter, the author summarizes common metabolic complications after ileal pouch surgery, including anemia, iron deficiency, vitamin B12 deficiency, vitamin D deficiency, bile salt malabsorption, bone loss, nephrolithiasis, and metabolic syndrome.
ANEMIA AND IRON DEFICIENCY Anemia is common in patients with ileal pouches, with a reported frequency of 17%–21% [3,4]. Iron deficiency can be seen in up to 56% (10 of 18 patients) of selected patient populations with pouches [5]. The etiology and pathogenesis of anemia in pouch patients are not clear. It is likely multifactorial. In this population, normocytic anemia occurred in 74% of patients, microcytic anemia in 24%, and macrocytic anemia in 2% [4]. Reported Pouchitis and Ileal Pouch Disorders. https://doi.org/10.1016/B978-0-12-809402-0.00013-7 © 2019 Elsevier Inc. All rights reserved.
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risk factors for anemia in patients with IPAA for underlying UC or FAP included the presence of J-pouch (vs. S- or Kock pouches) [4], or concurrent pouchitis, concurrent malignancy and desmoid tumors [3,5], Finally, anemia of chronic disease, which occurs in patients with chronic mucosal inflammation or small bowel intestinal bacterial overgrowth (SIBO) [6], may contribute to anemia seen in pouch patients. This author also noticed that patients with a large-volumed J-pouch and dilated afferent limb often have anemia. Iron deficiency is common in pouch patients in the presence or absence of anemia [5]. Postulated mechanisms of iron deficiency include poor oral intake, decreased absorption and utilization, intermittent blood loss, and increased requirements [7]. Similar to iron deficiency in non-pouch patients with inflammatory bowel disease (IBD), those with pouches have a poor tolerance of oral iron supplement, suggesting a major role played by the poor iron absorption and/or utilization, that is, iron deficiency/anemia of chronic diseases, in those patients. Attempts have been made to establish a connection between chronic blood loss and anemia. Unlike iron deficiency anemia (IDA) from chronic gastrointestinal (GI) bleeding in which patients normally tolerate oral iron supplement, pouch patients with anemia often have dyspepsia while taking oral iron. Although we occasionally see patients with slow, intermittent bleeding from cuffitis, suture line or anastomotic ulcers, or inflammatory polyps, we often are not able to identify bleeding lesions in the GI tract in the majority of patients with IDA. In fact, the author’s group has investigated the etiology of IDA in pouch patients, with an extensive work-up consisting of esophagogastroduodenoscopy, pouchoscopy, small bowel histology, capsule endoscopy, and celiac serology. We found definitive or possible etiology of IDA in only 29% of patients with ileal pouches [8]. These findings suggest that chronic GI bleeding is not a main etiology. De novo celiac disease following restorative proctocolectomy with IPAA has been described in case reports [9,10]. Since the establishment of the Center for Ileal Pouch Disorders at Cleveland Clinic in 2002, the author’s group have encountered 20 patients with de novo celiac disease. It is not clear whether the pouch surgery triggers the development of de novo celiac disease. It is interesting that a majority of those patients did not respond to gluten-free diet and required corticosteroid and/or immunomodulator therapy. Nevertheless in pouch patients with anemia and/or GI symptoms, we routinely screen for celiac disease.
VITAMIN B12 DEFICIENCY Vitamin B12 or cobalamin is a water-soluble vitamin which plays a key role in neural system as well as in the formation of blood. The physiology and pathophysiology of vitamin B12 absorption is complex. Vitamin B12 is released from dietary sources by acid and pepsin. R factor released from the saliva gland binds to free vitamin B12 protects it from degradation. In the duodenum, R factor is cleaved by proteases, allowing for vitamin B12 to bind to intrinsic factor produced by the stomach. The B12-intrinsic factor complex moves downward to the distal ileum where it is absorbed by ileal intrinsic factor receptors. Luminal bacteria can bind vitamin B12 and utilize it for in their metabolic activities, which can interfere with its normal transluminal uptake. It has been anticipated that patients with ileal pouches are at a high risk for vitamin B12 deficiency, as the pouch body created from the distal ileum inherently has fecal stasis, adaptive mucosal changes (colonic metaplasia), SIBO with subsequent microbial binding, and utilization of luminal vitamin B12, poor oral intake, and dietary restrictions. In a study of 171 with restorative proctocolectomy and IPAA, 25% of IPAA patients were found to have vitamin B12 deficiency but with normal Shilling’s tests [11]. Vitamin B12 deficiency in pouch patient can be corrected with oral supplementation, suggesting the role of poor intake in its development [11]. It appears that bile acids play a role in B12 absorption too. A separate study showed that 56% of pouch patients with vitamin B12 deficiency had bile salt deconjugation as measured by 14 C-glycocholic acid breath test and fecal bile acid level [12]. Those findings suggest that bacterial overgrowth or overload may be contributing factor [12]. While a large quantity of bacteria can bind vitamin B12 and prevent the latter from being absorbed, bacteria can also produce vitamin B12. It is not clear whether a long-term antibiotic or probiotic use in pouch patients has a positive or negative impact on B12 absorption. Small intestinal bacterial overgrowth is a norm in patients with ileal pouches. Contributing factors are anatomic and/or motility changes. The loss of the ileocecal valve during colectomy and ileal pouch construction leads to the reflux of pouch content to the proximal segment of small bowel. The current clinical standard practice in diagnosis of SIBO is glucose or lactulose breath tests and their use in the setting of the ileal pouch is controversial, as the breath tests standardized in patients with an intact colon. It is interesting that SIBO diagnosed by breath test was not reported to be associated with chronic pouchitis [13]. Whether the pouch surgery per se has an impact on vitamin B12 metabolism is not clear. In a cross-sectional study, vitamin B12 deficiency was found in 13% of UC patients before colectomy, and only 3% of patients with IPAA [14]. Possible explanations may be improved general nutritional status of the patients and increased bacterial production of vitamin B12
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in the pouch reservoir. Although villous atrophy or colonic metaplasia of the ileal pouch mucosa is common in patients with healthy or inflamed pouch [15,16]. Clinically significant vitamin B12 deficiency in pouch patients appears to be rare. The exceptions include strict vegetarians, concurrent gastric bypass surgery, and pernicious anemia.
BILE ACID MALABSORPTION Bile acids play a key role in fat and fat soluble vitamin absorption. Primary bile acids are produced in the liver and excreted in bile and secondary bile acids are formed from bacterial actions in the colon. They are preferentially (95%) absorbed in the terminal ileum through enterohepatic circulation. Bile acid malabsorption or bile acid diarrhea occurs when reabsorption is impaired due to ileal disease or ileal resection and bile acidss stimulate water secretion and intestinal motility. Bile acid metabolism and its impact on mucosal inflammation in patients with ileal pouches have been investigated. Aqueous phase fecal bile acids have been measured in patients following IPAA [17]. An alteration in the luminal bile acid pool may be involved in pouch inflammation [18]. In patients with IPAA, pool sizes of cholic acid (CA) and chenodeoxycholic acid (CDCA) were significantly lower than in healthy controls. In addition, fractional turnover rates of CA and CDCA were higher in those with IPAA than healthy controls. It is speculated that a reduced pool size of primary bile acids may contribute to the high frequency of cholesterol gallstones in patients with proctocolectomy and IPAA [19]. The change in bile acid pool in patients with IPAA is also evidenced by the investigation of patients with primary sclerosing cholangitis (PSC). PSC patients have known abnormalities in biliary structure and bile metabolism and flow. Biliary enrichment of ursodeoxycholic acid in pouch patients with PSC may be reduced [20]. Our group reported that pouch patients with PSC have a greater degree of endoscopic and histologic inflammation in the pouch body or distal afferent limb than pouch patients without PSC [21]. Clinically, almost all pouch patients with concurrent PSC have some degree of inflammation in the pouch and afferent limb and interestingly, their symptoms of diarrhea and abdominal cramps are often mild. This phenotype of disease has been labeled as “PSC-associated pouchitis/enteritis”, a part of immune-mediated pouchitis [22]. Inflammatory changes in the pouch are postulated to manifest as changes in bile acid conjugation and dehydroxylation [19],rather than changes in bile acid composition [23]. Villous atrophy, colonic metaplasia, and chronic pouchitis may result from or result in decreased bile salt absorption [24,25]. Diseased ileum or pouch mucosa can impair bile acid and fat absorption, as evidenced by a study showing abnormal 75selenium homotaurocholate uptake test in 7 of 8 pouch patients, and by analysis of abnormal 14C triolein breath test in 3 of 8 pouch patients [26].
VITAMIN D DEFICIENCY Vitamin D, a fat soluble vitamin is primarily absorbed in the duodenum and jejunum. It is hydroxylated in the liver to form 25-OH vitamin D and in the kidney to form 1, 25-OH vitamin D. It appears that the association between vitamin D metabolism and IBD is reciprocal. Chronic gut inflammation may interfere with vitamin D metabolism and deficiency in vitamin D, an “anti-inflammatory” substance, may increase the risk for the development of inflammation. Vitamin D receptor (VDR) is an important component in maintaining mucosal integrity [27,28], and its abnormality has been implicated in the pathogenesis from dextran sulfate sodium. In contrast, VDR knockout mice were prone to develop severe colitis [25]. In other murine models, inflammation of the GI tract develops in VDR knockout animals [26]. In a study of 188 patients with pediatric-onset UC of whom 33 (18%) underwent restorative proctocolectomy and IPAA, the investigators reported that preoperative vitamin D deficiency (≤20 ng/mL) was associated with an increased hazard ratio of 4.4 for the risk of pouchitis [29]. Clinically, vitamin D deficiency is common in patients with IBD [30],with the lowest level seen in those with severe disease [31,32]. IBD patients with vitamin D deficiency had quality of life (QOL), independently from the disease activity [29]. In an earlier study of 107 patients with ileal pouches, the frequency of vitamin D deficiency was reported in 11% of patients [15]. In contrast, a cohort study of 157 patients from the Cleveland Clinic showed that the frequency of vitamin D deficiency was 69% [33]. Similarly, a recent letter to the editor reported vitamin D deficiency in 80% of patients with IPAA [34]. Interestingly, anemia was found to be an independent risk factor for vitamin D deficiency. The geographic location of patients, season of measurement, and medications were not found to be associated with vitamin D deficiency in those patients [30]. In addition, there was no significant association found between pouch inflammation and vitamin D deficiency [30]. The presence of concurrent PSC, however, in pouch patients posed a risk for vitamin D deficiency [35]. It is not clear whether the commonly encountered low vitamin D level has any adverse impact on the pouch outcomes. However, we speculate that low vitamin D at least can affect the bone metabolism in pouch patients.
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BONE LOSS AND BONE FRACTURE Bone loss is common in patients with IBD and patients with IPAA are not an exception. In a study of 53 patients from St Mark’s Hospital, London, the frequency of osteopenia and osteoporosis was reported to be 43% and 13%, respectively [36]. In a separate study of 327 pouch patients from the Cleveland Clinic, 105 patients (32%) had low bone mineral density (BMD) with either osteoporosis or osteopenia [37]. The reported incidence of fragility fractures ranged from 7% to 15% [34,38]. Factors associated with a low BMD were found to be advanced age, low body mass index, and no calcium supplementation. Interestingly, factors related to the pouch condition itself, such as the presence of chronic pouchitis and CD of the pouch were not found to be associated with the bone loss [34]. The construction of an ileal pouch, with or without inflammatory conditions of the reservoir may or may not have a beneficial or detrimental impact on bone metabolism. It is known that patients with UC are at risk for bone loss [39]. However, there are conflicting reports on the impact of colectomy and IPAA on BMD. In a study of 267 patients with UC and IPAA and 119 patients with UC without IPAA, 83 (31.1%) and 18 (15.1%) had a low BMD, respectively. Interestingly, 64 UC patients with IPAA (24.0%) were on corticosteroid therapy postoperatively, as compared to 93 (78.2%) in the nonpouch UC patients. The presence of IPAA per se (odds ratio [OR]:6.02; 95% confidence interval [CI], 2.46–14.70) was an independent risk factor for low BMD [40]. A separate longitudinal study showed that BMD values increased over time after IPAA surgery [39]. The etiology and pathogenesis of bone loss in IPAA patients are multifactorial. In addition to the reported risk factors such as advanced age, a low body mass index [16,34,37], and lack of calcium supplementation [34], vitamin D and parathyroid hormone should play a role. The adaptive change of the small bowel and pouch mucosa from fecal stasis in pouch patient may also be a contributing factor. In fact, 37% of IPAA patients with villous atrophy had osteopenia, compared to 0% with normal villous structure [16]. The lowest BMD scores were found in patients with inflammation in the afferent limb [16]. The presence of inflammation is associated with circulating cytokines such as interleukins (IL-1 and IL-6) and tumor necrosis factor-α, which stimulate osteoclast activity and lead to bone reabsorption and bone loss [41]. Supplementation of calcium and vitamin D has been shown to increase BMD scores in patients with IBD [42]. Although an increased inflammatory activity of the pouch has been associated with a lower BMD, the clear connection between pouchitis and vitamin D deficiency remains to be determined. There are no published on improvement of BMD by anti-inflammatory therapy in pouch patients. Of interest, the frequent bone loss does not translate an increased risk for bone fracture. In fact, fracture risk after IPAA was shown to be reduced as compared with UC patients without IPAA. In a study of 1757 IPAA patients, as compared with 8785 UC controls, from a national cohort of Danish UC patients, the adjusted hazard ratio of fracture was 0.49 (95% CI: 0.43; 0.55) [43].
NEPHROLITHIASIS Overall QOL is often improved following IPAA [44,45], symptomatic nephrolithiasis after the surgery can compromise the gain in QOL. The prevalence of nephrolithiasis has been estimated at 5% of the general population [46], and 7% in patients with IBD [47]. The purported risk factors associated with nephrolithiasis in IBD patients have been postulated including diarrhea, dehydration, and low urine volume, pH, citrate, and magnesium, and elevated urine oxalate [48]. The author’s group reported that 37% of patients with IPAA in the Center for Ileal Pouch Disorders at the Cleveland Clinic had nephrolithiasis. The majority of these patients had symptomatic stones. The presence of extraintestinal manifestations, non-use of antibiotics, and lower serum bicarbonate levels were found to be risk factors for developing kidney stones [44]. Our group prospectively studied 40 patients with or without nephrolithiasis. There were no significant differences in serum electrolytes, vitamin D, parathyroid hormone, and kidney function tests between the study (n=20) and control (n=20) groups. Patients in the nephrolithiasis group were found to have a higher 24-h urine supersaturation of calcium oxalate and calcium phosphate than controls. Nineteen (95%) patients in the study group were symptomatic due to nephrolithiasis with several requiring procedural intervention for treatment, including ureteroscopy in three (15%) patients, lithotripsy in five (25%), and percutaneous surgery in one (5%) [49]. Adequate oral hydration is critical for prevention of nephrolithiasis in patients with IBD, ileal pouches, or stomas. The management of nephrolithiasis and bone loss in patients with the ileal pouch can be contradictory, that is, supplement of oral calcium and vitamin D.
FAT METABOLISM It is known that obese patients undergoing restorative proctocolectomy with IPAA pose greater technical challenges for surgeons and have a great risk of postoperative complications [50,51]. Excessive weight gain and fat accumulation may
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also have an adverse impact on the long-term outcome of the pouch. Abnormal fat metabolism in patients after the ileal pouch can be manifested by fat malabsorption and fat gain. Fat malabsorption appeared to be associated with bile acid malabsorption. Fat absorption was reported to be reduced in patients with IPAA as compared to those with ileostomies [52]. In patients with healthy or diseased pouch construction, the presumed fecal stasis with bacterial overload could lead to bile salt deconjugation and a decreased absorption as measured by 75selenium homotaurocholate, as compared to those with healthy pouches [24]. Clinically, decreased serum total low density lipoprotein cholesterol levels, and triglycerides have been reported in patients with IPAA [53]. While patients with surgical procedure-associated, mechanical disorders of the pouch (such as presacral sinus and afferent limb syndrome) or CD of the pouch are often underweight, patients with a healthy pouch often gained weight after the pouch construction from generally improved health and oral intake. However, the author’s group found that an excessive weight gain is associated with a higher risk pouch failure from pouch sinus and chronic pouchitis [54]. It is speculated that central obesity or gain in the mesenteric fat, rather than cutaneous fat, is the main contributing factor [55].
SUMMARY AND RECOMMENDATION Long-term metabolic consequences have increasingly been recognized in patients with ileal pouches. These include anemia, iron deficiency, preexisting, or de novo celiac disease, vitamin B12 deficiency, bile salt malabsorption, vitamin D deficiency, bone, and nephrolithiasis. The etiology and pathogenesis are likely multifactorial. Those adverse metabolic sequelae can occur in patients without pouch inflammation. Clinicians should be aware of these conditions in patients with healthy and diseased pouches, so that appropriate screening and patient counseling may take place.
REFERENCES [1] Shen B, Remzi FH, Lavery IC, Lashner BA, Fazio VW. A proposed classification of ileal pouch disorders and associated complications after restorative proctocolectomy. Clin Gastroenterol Hepatol 2008;6:145–58. [2] Buckman SA, Heise CP. Nutrition considerations surrounding restorative proctocolectomy. Nutr Clin Pract 2010;25:250–6. [3] Tiainen J, Matikainen M. Long-term clinical outcome and anemia after restorative proctocolectomy for ulcerative colitis. Scand J Gastroenterol 2000;35:1170–3. [4] Oikonomou IK, Fazio VW, Remzi FH, Lopez R, Lashner BA, Shen B. Risk factors for anemia in patients with ileal pouch–anal anastomosis. Dis Colon Rectum 2007;50:69–74. [5] Pastrana RJ, Torres EA, Arroyo JM, Rivera CE, Sánchez CJ, Morales L. Iron-deficiency anemia as presentation of pouchitis. J Clin Gastroenterol 2007;41:41–4. [6] Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011–23. [7] M’Koma AE, Wise PE, Schwartz DA, Muldoon RL, Herline AJ. Prevalence and outcome of anemia after restorative proctocolectomy: a clinical literature review. Dis Colon Rectum 2009;52:726–39. [8] Shen B, Remzi FH, Santisi J, Lashner BA, Brzezinski A, Fazio VW. Application of wireless capsule endoscopy for the evaluation of iron anemia in patients with ileal pouches. J Clin Gastroenterol 2008;42:897–902. [9] Shen L, Lian L, Goldblum JR, Remzi FH. Development of de novo celiac disease after restorative proctocolectomy and ileal pouch–anal anastomosis. Inflamm Bowel Dis 2009;15:1131–2. [10] Tyler AD, Murdoch TB, Riddell RH, Silverberg MS. Celiac disease detected by pouch biopsy of a patient with ileal pouch-anal anastomosis. Am J Gastroenterol 2011;106:1367–8. [11] Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Color Dis 2007;9:562–6. [12] Hylander E, Rannerm T, Hegnhøj J, Kirkegarrd P, Thale M, Jarnum S. Absorption studies after ileal J-pouch anastomosis for ulcerative colitis: a prospective study. Scand J Gastroenterol 1991;26:65–72. [13] Lisowska A, Banasiewicz T, Marciniak R, et al. Chronic pouchitis is not related to small intestine bacterial overgrowth. Inflamm Bowel Dis 2008;14:1102–4. [14] M’Koma AE. Follow-up results of hematology data before and after restorative proctocolectomy: clinical outcome. Dis Colon Rectum 1994;37:932–7. [15] Kuisma J, Nuutinen H, Luukkonen P, Järvinen H, Kahri A, Färkkilä M. Long term metabolic consequences of ileal pouch–anal anastomosis for ulcerative colitis. Am J Gastroenterol 2001;96:3110–6. [16] Kuisma J, Luukkonen P, Järvinen H, Kahri A, Färkkilä M. Risk of osteopenia after proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis. Scand J Gastroenterol 2002;37:171–6. [17] Sandborn WJ, Tremaine WJ, Batts KP, et al. Fecal bile acids, short-chain fatty acids, and bacteria after ileal pouch-anal anastomosis do not differ in patients with pouchitis. Dig Dis Sci 1995;40:1474–83. [18] Hill MJ, Owen RW. Fecal bile acids in pouch and pouchitis patients: pouchitis workshop. Int J Color Dis 1989;4:221–2. [19] Gotthardt DN, Sauer P, Schaible A, Stern J, Stiehl A, Beuers U. Kinetics of primary bile acids in patients after proctocolectomy and ileal pouch-anal anastomosis. Digestion 2014;90:27–32.
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[20] Rost D, Rudolph G, Kloeters-Plachky P, Stiehl A. Effect of colitis and ileoanal pouch on biliary enrichment of ursodeoxycholic acid in primary sclerosing cholangitis. Dig Dis Sci 2006;51:618–22. [21] Shen B, Bennett AE, Navaneethan U, et al. Primary sclerosing cholangitis is associated with endoscopic and histologic inflammation of the distal afferent limb in patients with ileal pouch-anal Anastomosis. Inflamm Bowel Dis 2011;17:1890–900. [22] Shen B. Pouchitis: what every gastroenterologist needs to know. Clin Gastroenterol Hepatol 2013;11:1538–49. [23] Becker JM, Man CH, Hocking J. Fecal bile acid composition with patients with pouchitis following colectomy and ileal pouch-anal anastomosis. Gastroenterology 1994;106:A650. [24] Nicholls RJ, Belliveau P, Neill M, Wilks M, Tabaqchali S. Restorative proctocolectomy with ileal reservoir: a patholophysiological assessment. Gut 1981;22:462–8. [25] Christl SU, Scheppach W. Metabolic consequences of total colectomy. Scand J Gastroenterol Suppl 1997;222:20–4. [26] Fiorentini MT, Locatelli L, Ceccopieri B, et al. Physiology of ileoanal anastomosis with ileal reservoir for ulcerative colitis and adenomatosis coli. Dis Colon Rectum 1987;30:267–72. [27] Kong J, Zhang Z, Musch MW, et al. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 2008;294:G208–16. [28] Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT. A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol 2003;17:2386–92. [29] Rinawi F, Assa A, Eliakim R, et al. Predictors of pouchitis after ileal pouch-anal anastomosis in pediatric-onset ulcerative colitis. Eur J Gastroenterol Hepatol 2017;29:1079–85. [30] Silvennoinen J. Relationships between vitamin D, parathyroid hormone and bone mineral density in inflammatory bowel disease. J Intern Med 1996;239:131–7. [31] Joseph AJ, George B, Pulimood AB, Seshadri MS, Chacko A. 25 (OH) vitamin D level in Crohn’s disease: association with sun exposure & disease activity. Indian J Med Res 2009;130:133–7. [32] Ulitsky A, Ananthakrishnan AN, Naik A, et al. Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life. JPEN J Parenter Enteral Nutr 2011;35:308–16. [33] Khanna R, Wu X, Shen B. Low levels of vitamin D are common in patients with ileal pouches irrespective of pouch inflammation. J Crohns Colitis 2013;7:525–33. [34] Miller HL, Farraye FA, Coukos J, et al. Vitamin D deficiency and insufficiency are common in ulcerative colitis patients after ileal pouch-anal anastomosis. Inflamm Bowel Dis 2013;19:E25–6. [35] Fialho A, Fialho A, Kochhar G, Shen B. The presence of primary sclerosing cholangitis in patients with ileal pouch anal-anastomosis is associated with an additional risk for vitamin D deficiency. Gastroenterol Rep (Oxf) 2016;4:320–4. [36] McLaughlin SD, Perry-Woodford ZL, Clark SK, et al. Osteoporosis in patients over 50 years of age following restorative proctocolectomy for ulcerative colitis: is DXA screening warranted? Inflamm Bowel Dis 2010;16:250–5. [37] Shen B, Remzi FH, Oikonomou IK, et al. Risk factors for low bone mass in patients with ulcerative colitis following ileal pouch-anal anastomosis. Am J Gastroenterol 2009;104:639–46. [38] Abitbol V, Roux C, Guillemant S, et al. Bone assessment in patients with ileal pouch-anal anastomosis for inflammatory bowel disease. Br J Surg 1997;84:1551–4. [39] Schulte C, Dignass AU, Mann K, Goebell H. Reduced bone mineral density and unbalanced bone metabolism in patients with inflammatory bowel disease. Inflamm Bowel Dis 1998;4:268–75. [40] Navaneethan U, Shen L, Venkatesh PG, et al. Influence of ileal pouch anal anastomosis on bone loss in ulcerative colitis patients. J Crohns Colitis 2011;5:415–22. [41] Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995;332:305–11. [42] Abitbol V, Mary JY, Roux C, et al. Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluoride. Aliment Pharmacol Ther 2002;16:919–27. [43] Christensen AM, Brandsborg S, Vestergaard P, Laurberg S. Comparison of fracture risk between patients with ileal pouch-anal anastomosis for ulcerative colitis and the general population. J Crohns Colitis 2014;8:107–12. [44] Martin A, Dinca M, Leone L, et al. Quality of life after proctocolectomy and ileo-anal anastomosis for severe ulcerative colitis. Am J Gastroenterol 1998;93:166–9. [45] Scarpa M, Angriman I, Ruffolo C, et al. Health-related quality of life after restorative proctocolectomy for ulcerative colitis: long-term results. World Surg 2004;28:124–9. [46] Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC. Time trends in reported prevalence of kidney stones in the United States: 19761994. Kidney Int 2003;63:1817–23. [47] Gelzayd EA, Breuer RI, Kirsner JB. Nephrolithiasis in inflammatory bowel disease. Am J Dig Dis 1968;13:1027–34. [48] Mukewar S, Hall P, Lashner BA, Lopez R, Kiran RP, Shen B. Risk factors for nephrolithiasis patients with Ileal pouches. J Crohns Colitis 2013;7:70–8. [49] Arora Z, Mukewar S, Lopez R, Camino D, Shen B, Hall P. Etiopathogenesis of nephrolithiasis in ulcerative colitis patients with ileal pouch-anal anastomosis. Inflamm Bowel Dis 2017;23:840–6. [50] Klos CL, Safar B, Jamal N, et al. Obesity increases risk for pouch-related complications following restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). J Gastrointest Surg 2014;18:573–9.
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[51] Kiran RP, Remzi FH, Fazio VW, et al. Complications and functional results after ileoanal pouch formation in obese patients. J Gastrointest Surg 2008;12:668–74. [52] Bain IM, Mostafa AB, Harding LK, Neoptolemos JP, Keighley MR. Bile acid absorption from ileoanal pouches using enema scintigraphy. Br J Surg 1995;82:614–7. [53] Hakala K, Vuoristo M, Luukkonen P, Järvinen HJ, Miettinen TA. Impaired absorption of cholesterol and bile acids in patients with an ileoanal anastomosis. Gut 1997;41:771–7. [54] Wu XR, Zhu H, Kiran RP, Remzi FH, Shen B. Excessive weight gain is associated with an increased risk for pouch failure in patients with restorative proctocolectomy. Inflamm Bowel Dis 2013;19:2173–81. [55] Shen B. Problems after restorative proctocolectomy: assessment and therapy. Curr Opin Gastroenterol 2016;32:49–54.