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Small Bowel Perforation in Roux-en-Y Gastric Bypass (RYGB) Secondary to Apolipoprotein A-IV (AApoA-IV) Type Amyloidosis

Small Bowel Perforation in Roux-en-Y Gastric Bypass (RYGB) Secondary to Apolipoprotein A-IV... Background ApoA‐IV amyloidosis is a rare disease that involves the deposition of ApoA-IV protein aggregates in tissues. It commonly presents as cardiac or renal disease, but can, in rare cases, cause small bowel perforation. Methods This study describes a case of ApoA-IV type amyloidosis causing small bowel perforation after conversion of a sleeve gastrectomy (SG) into a RYGB in a Crohn’s disease (CD) and rheumatoid arthritis (RA) patient. It also considers the indications for bariatric and anti-reflux surgery in the setting of co-morbid inflammatory bowel disease (IBD), gastro- oesophageal reflux disease (GORD), and obesity. Results Obesity can reduce the efficacy of IBD medications and drives a pro-inflammatory state that may worsen IBD, however IBD patients present an operative challenge due to risk of more intestinal adhesions, potential intolerance to intestinal bypass, and risk of affecting options for future bowel resections if required. SG is often chosen over RYGB for CD patients due to limited short-term complications. However, when considering co-morbid GORD, the long-term risk of medication resistant GORD, erosive oesophagitis, and Barrett’s oesophagus with SG is significant, especially given that SG is an irreversible procedure. Conclusion There is growing evidence that bariatric surgery in IBD patients is both safe and effective, however the decision to perform bariatric surgery in an IBD patient involves consideration of the intricate interplay between obesity and IBD. Keywords Amyloidosis · Crohn's Disease · Ulcerative Colitis · Inflammatory Bowel Disease · Bariatric Surgery Background Amyloidosis is a heterogenous group of diseases involving abnormal protein deposition. Though rare, one must consider Key Points amyloidosis as a potential cause of small bowel perforation • This study describes a rare case of ApoA-IV type amyloidosis causing small bowel perforation. in patients with IBD. There is an increasing prevalence of • Bariatric surgery in IBD patients is both safe and effective. obesity among IBD patients, estimated at approximately • The decision to perform bariatric surgery in an IBD patient 15–30%, as well as a growing number of bariatric operations involves consideration of the intricate interplay between co- being performed [1–5]. Bariatric surgery is increasingly morbid obesity and IBD. • SG is often chosen over RYGB in the setting of CD, but being offered to patients with co-morbid obesity and IBD, the long-term risk of medication resistant GORD, erosive due to mounting evidence of its safety and efficacy in this oesophagitis, and Barrett’s oesophagus (BE) with SG must be cohort [4, 6–11]. Though bearing significant potential ben- considered. efit, the decision to perform bariatric surgery in IBD patients * Mona Zhi Ling Mai Jiang is a balance of multiple factors. This study describes a rare [email protected] case of apolipoprotein A-IV (AApoA-IV) type amyloidosis Stefaan De Clercq causing small bowel perforation post-RYGB and examines [email protected] the considerations involved when choosing to perform bari- atric surgery on an IBD patient. St Vincent’s Hospital, Melbourne, Australia Friendly Society Private Hospital, Bundaberg, Australia Vol.:(0123456789) Obesity Surgery Case Presentation A woman in her 50s presented approximately 2 years post-SG with a hiatal hernia and severe mixed acid and biliopancre- atic reflux. Her symptoms, including progressively worsen- ing nausea, burping, and burning epigastric pain, not con- trolled by proton pump inhibitors and anti-emetics, resulted in extremely poor quality of life. Her past medical history was significant for CD, first diagnosed in 2022 and managed with adalimumab, as well as RA, diagnosed approximately in the 1980s and managed with methotrexate and non-steroidal anti- inflammatories. Other medical history included GORD, iron deficiency anaemia, laparoscopic cholecystectomy, caesarean section, and previous bilateral total hip replacements with multiple revisions for a delayed diagnosis of hip dysplasia. SG was initially chosen in order to prevent short-term, medication-associated complications related to RYGB, as was commonly suggested in the literature at that time. How- ever, recent literature demonstrates that complication rates after various weight loss surgeries are comparable between IBD and non-IBD patients (see ‘Discussion’ for further details). Given the absence of a fundus, a hiatal hernia repair with fundoplication was not possible. Therefore, a decision was made to convert her SG to a RYGB. The preoperative screening upper and lower endoscopies demonstrated a 4 cm mixed hiatal hernia, bilious fluid in the stomach, gastritis, Fig. 1 Intraoperative images from conversion of SG to RYGB. A mild diverticulosis, and some small hyperplastic colonic pol- Hiatal hernia. B Distal RYGB anastomosis yps. Coeliac disease, disaccharidase deficiency, endocrine disorders, Helicobacter pylori infection, and psychological a transition point near the distal anastomotic site. She was admit- contraindications were excluded pre-operatively. Adali- ted to hospital with a presumed diagnosis of adhesional small mumab was discontinued perioperatively. bowel obstruction and returned to theatre for laparoscopic adhe- Intraoperatively, a 3.5 m common limb was designed, as siolysis and revision of the distal anastomosis. Intra-operatively, opposed to the usual 3 m, to accommodate a possible future a limited, contained small bowel perforation was noted at the resection of the terminal ileum (see Fig.  1). The periop- distal anastomosis, with surrounding dense adhesions. The ini- erative course of this conversion was unremarkable, and a tial distal anastomosis was resected and sent for histopathology, short segment of resected small bowel, from in between the with a new distal anastomosis formed via jejuno-jejunostomy two anastomoses, was confirmed to be viable with no histo - (see Fig. 2). Her post-operative recovery was unremarkable, and logical abnormalities. The patient was discharged on day 3 she was discharged on day 5 after the revision operation. post-operatively and was progressing well on review in the On histopathological analysis, the small bowel mucosa surgical clinic, 1 week post-operatively. showed a site of perforation and was otherwise macroscopi- She represented to the emergency department 15 days post- cally unremarkable. Microscopically, the resected margins operatively, with progressively worsening epigastric and left- were viable. There was congophilia of the small arteries and sided colicky abdominal pain, nausea and vomiting. Her tem- arterioles of the submucosa, with apple green birefringence perature was 36.4 °C, and her observations were within normal on polarisation of the slide (Congo red stain). There was limits. She had epigastric and left upper quadrant tenderness on metachromasia on crystal violet stain (see Fig.  3). These palpation, without signs of guarding, rigidity, or peritonism. She microscopic changes were consistent with amyloidosis, and had a neutrophilia of 11.65 × 10⁹/L with a total white cell count further amyloid subtyping via liquid chromatography–mass of 14.3 × 10⁹/L. There was an associated elevated platelet count spectrometry favoured AApoAIV type amyloidosis. of 460 × 10⁹/L and elevated C-reactive protein of 44 mg/L. Her She was reviewed in the surgical clinic 2 weeks after the routine blood biochemistry was otherwise unremarkable. revision operation and was recovering well. She had fol- Computed tomography (CT) abdomen and pelvis showed low-up in the amyloidosis clinic, with no evidence of the distension of jejunal bowel loops in the left upper quadrant, with Obesity Surgery more common cardiac or renal amyloid complications on screening investigations. On phone review 16 months after the revision operation, she described minimal reflux-related symptoms; she was able to return to her usual work and per- sonal duties, but continues to have persistent fatigue. Discussion Amyloidosis comprises a group of heterogeneous diseases, involving deposition of protein aggregates in various tissues [12]. It is subdivided by type according to the pathogenic fibril precursor protein [13]. Reactive or serum amyloid A protein (AA) amyloidosis is a common form of amyloidosis and occurs secondary to elevated serum amyloid A protein, which is seen in chronic inflammatory states [14]. Its syn- thesis in hepatocytes is regulated primarily by IL-1 and IL-6, with SAA levels increasing in response to inflammation and remaining elevated until the inflammation resolves [13]. In this case, our patient had CD and RA, both of which can cause AA amyloidosis, although notably, this was not the amyloidogenic protein in question. Systemic AA amyloido- sis secondary to IBD has an estimated prevalence of 0.53% and occurs more commonly in CD than ulcerative colitis (UC) [13, 15, 16]. This may be explained by the more pro- nounced acute phase response seen in CD, which may be Fig. 2 Intraoperative images from revision of RYGB, with resection related to its higher prevalence of suppurative features [13]. of contained perforation and formation of jejunojejunostomy. A Dis- tal RYGB anastomosis. B Exposed small bowel perforation Additionally, surgical resection can act as definitive man - agement for UC, leading to improved long-term control of systemic inflammation, whereas the same is not possible in CD [13]. However, systemic AA amyloidosis in the setting of IBD commonly presents as renal and cardiac disease, as opposed to gastrointestinally [17]. Fig. 3 A representative section of small bowel wall, showing green birefringence on polarisa- tion (Congo red), consistent with amyloidosis Obesity Surgery AA amyloidosis can be treated through control of the BMI [29]. SG can also be performed in patients where intesti- underlying inflammatory process. A case study by Prayman nal bypass is a relative contraindication, such as those on anti- et al. noted renal impairment or proteinuria in all included inflammatory medications or patients with IBD [29]. However, patients, with an association between poorly controlled IBD, SG is irreversible and is less effective than RYGB for sustained raised inflammatory markers, and progressive renal impair - weight loss and remission of obesity-associated comorbidities ment [13]. Consequently, reduced inflammation and lowered [29, 30]. Additionally, the effect of SGs on GORD is variable; production of SAA can also lead to amyloid resorption via some studies show improvement in GORD, likely secondary macrophage-related activity, although the exact mechanism to weight loss and reduced gastric acid secretion, while oth- is unclear [13]. In this case, the patient was on adalimumab, ers indicate worsening GORD or de novo GORD post-SG [29, which was ceased pre-operatively. Adalimumab is a human- 31]. A meta-analysis by Yeung et al. has estimated rates of de ised immunoglobulin  G1 monoclonal antibody directed novo GORD post-SG at 23%, oesophagitis at 28%, and Barrett’s against tumour necrosis factor-alpha (anti-TNF-alpha) [18]. oesophagus (BE) at 6% [32]. A prospective randomised study A study by Kuroda et al. showed a reduction in gastroduode- by Genco et al. demonstrated that the cumulative incidence of nal AA amyloid deposits upon successful treatment with anti- oesophagitis post-SG was up to 74.7% 5 years post-operative, TNF-alpha therapy, in patients with rheumatoid arthritis [19]. often with associated biliopancreatic reflux, generating BE with However, this was not the amyloidogenic protein found here. an incidence of 8% [29]. Severe medication-resistant GORD is This case demonstrated gastrointestinal ApoA-IV type amy- the most common indication for revision surgery post-SG [32]. loidosis, a rare and under-investigated form of amyloidosis. Additionally, SG eliminates the possibility of fundoplication ApoA-IV is a 46kD protein that is secreted from the small should severe GORD occur post-operatively. Therefore, RYGB bowel in response to lipid absorption and chylomicron forma- is still commonly considered the gold standard for management tion; however, its specific biological role has yet to be identified of co-morbid obesity and GORD [31]. [20, 21]. It may have antioxidant, anti-inflammatory and athero- The decision to perform bariatric and anti-reflux sur - protective functions [22]. Plasma levels of ApoA-IV increase gery in IBD patients is a complex one, taking into account with age; however, it is unclear if high levels of ApoA-IV leads the risk of operative complications, the risks of long-term to ApoA-IV amyloidosis [23, 24]. Analysis of patients attending GORD, and the benefit of weight loss on both general health the UK NHS National Amyloidosis Centre revealed 15 cases of as well as the clinical course of IBD. There is evidence that ApoA‐IV amyloidosis, with only a singular case of duodenal bariatric surgery is both safe and effective in IBD patients, ApoA‐IV amyloidosis [25]. The Mayo Clinic’s review of their with numerous studies showing no difference in weight loss, mass spectrometry database indicated that 0.45% of all 9673 quality of life, or postoperative complications between IBD cases of amyloidosis from all organs were ApoA‐IV amyloi- and non-IBD cohorts [6, 7, 9–11, 33]. Some studies noted dosis [24]. In our search of the literature, no other documented some variations on subgroup analysis. A systematic review cases of jejunal ApoA‐IV amyloidosis were found. ApoA‐IV by Aziz et al. found that post-operative bleeding and wound amyloidosis is typically systemic, with renal and cardiac mani- infections occurred at higher rates in IBD patients [10]. In a festations being the most common [26]. Renal findings include cohort study by Wallhuss et al., higher rates of postoperative progressively declining renal function with minimal proteinu- complication were noted in RYGB patients with UC, and ria [24]. Renal biopsies showed amyloid deposits in the renal higher re-admission rates were noted among CD patients; medulla for all cases, with some cases also having peritubular weight loss was found to be marginally better with RYGB amyloid deposits; the renal cortex was spared, and there was in IBD patients [7]. Additionally, in the setting of comorbid no interstitial inflammation [24, 27]. Cardiac manifestations of IBD and obesity, successful weight loss has been associ- ApoA‐IV amyloidosis included left ventricular outflow tract ated with fewer IBD-related complications [8]. This may obstruction and coronary artery disease [28]. Histopathologi- be related to the reduced efficacy of IBD medications in the cal samples of cardiac tissue showed obstructive microvascular setting of obesity [34, 35]. A case series by Aminian et al. amyloidosis in all cases and nodular interstitial deposition in noted improvement in IBD symptoms in 9 of 10 patients post some cases [28]. Unlike other forms of amyloidosis, ApoA‐IV weight loss due to bariatric surgery [4]. This may be due to amyloidosis has no specific treatments [24]. the pro-inflammatory nature of obesity, with over-expression In this case study, SG was the initially chosen bariatric pro- of IL-6, TNF-alpha, and adipokines in visceral and mesen- cedure, however the patient developed medication resistant teric fat [4]. It follows that weight loss may reduce the pro- GORD, necessitating conversion to RYGB. SG is the most com- duction of obesity-related pro-inflammatory cytokines and monly performed bariatric surgery [5]. It is especially favoured therefore reduce IBD disease activity [4]. A meta-analysis due to the short operative time and relative technical simplic- by Garg et al. noted that only 11% of patients had increasing ity, which is advantageous in patients with significant respira- IBD medication requirements post-bariatric surgery, with tory or cardiovascular comorbidities, or those with extensive the majority experiencing no change, and 46% experiencing adhesions or a restricted operative field due to extremely high a reduction in IBD medication [9]. Obesity Surgery Author Contribution M.J. wrote the main manuscript text and pre- 8. Braga Neto MB, Gregory MH, Ramos GP, et al. Impact of bariat- pared Figs. 1–3. S.D. conceptualised the study and contributed data. ric surgery on the long-term disease course of inflammatory bowel All authors reviewed the manuscript. disease. Inflamm Bowel Dis. 2020;26:1089–97. 9. Garg R, Mohan BP, Ponnada S, et al. Safety and efficacy of bari- Funding Open access funding provided by St Vincent’s Hospital Mel- atric surgery in inflammatory bowel disease patients: a systematic bourne, Victorian Health Libraries Consortium (VHLC). review and meta-analysis. OBES SURG. 2020;30:3872–83. 10. Aziz M, Haghbin H, Sharma S, et al. Safety of bariatric surgery Data Availability No datasets were generated or analysed during the in patients with inflammatory bowel disease: a systematic review current study. and amet -sisyaaln . Clin Obes. 2020;10:e12405. 11. Hudson JL, Barnes EL, Herfarth HH, et al. Bariatric surgery is a safe and effective option for patients with inflammatory bowel Declarations diseases: a case series and systematic review of the literature. Inflamm Intest Dis. 2018;3:173–9. Ethics Approval and Consent to Participate All procedures performed 12. Bustamante JG, Zaidi SRH. Amyloidosis. StatPearls [Internet]. in this study were in accordance with the ethical standards of the insti- Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 tutional ethics committee and with the 1964 Helsinki declaration and Feb 04]. Available from: http:// www. ncbi. nlm. nih. gov/ books/ its later amendments. Informed consent was obtained from the study NBK47 0285/. participant. 13. Sattianayagam PT, Gillmore JD, Pinney JH, et  al. Inflamma- tory bowel disease and systemic AA amyloidosis. Dig Dis Sci. Competing Interest The authors declare no competing interests. 2013;58:1689–97. 14. Dahiya DS, Kichloo A, Singh J, et al. Gastrointestinal amyloido- Open Access This article is licensed under a Creative Commons Attri- sis: A focused review. WJGE. 2021;13:1–12. bution 4.0 International License, which permits use, sharing, adapta- 15 Tosca Cuquerella J, Bosca-Watts MM, Anton Ausejo R, et al. tion, distribution and reproduction in any medium or format, as long Amyloidosis in inflammatory bowel disease: a systematic review as you give appropriate credit to the original author(s) and the source, of epidemiology, clinical features, and treatment. J Crohn’s Coli- provide a link to the Creative Commons licence, and indicate if changes tis. 2016;10(10):1245–53. were made. The images or other third party material in this article are 16. Hamamoto Y, Kido K, Kawamura M, et al. Subclinical amyloid included in the article’s Creative Commons licence, unless indicated deposition in inflammatory bowel diseases: a two hospital study. otherwise in a credit line to the material. If material is not included in Pathol - Res Pract. 2024;264:155682. the article’s Creative Commons licence and your intended use is not 17. Gill VS, Boddu SP, Abujbarah S, et al. Secondary amyloidosis in permitted by statutory regulation or exceeds the permitted use, you will inflammatory bowel disease patients: findings from three tertiary need to obtain permission directly from the copyright holder. To view a medical centers. Clin J Gastroenterol. 2024;17:844–53. copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 18. Fikri-Benbrahim O, Rivera-Hernández F, Martínez-Calero A, et al. Treatment with adalimumab in amyloidosis secondary to rheumatoid arthritis: two case reports. Nefrologia. 2013;33:404–9. 19. Kuroda T, Wada Y, Kobayashi D, et  al. Effective anti-TNF-α therapy can induce rapid resolution and sustained decrease References of gastroduodenal mucosal amyloid deposits in reactive amy- loidosis associated with rheumatoid arthritis. J Rheumatol. 1. Steed H, Walsh S, Reynolds N. A brief report of the epidemiol- 2009;36:2409–15. ogy of obesity in the inflammatory bowel disease population of 20. Elshourbagy NA, Walker DW, Paik YK, et  al. Structure and Tayside. Scotland Obes Facts. 2009;2:370–2. expression of the human apolipoprotein A-IV gene. J Biol Chem. 2. Flores A, Burstein E, Cipher DJ, et  al. Obesity in inflamma- 1987;262:7973–81. tory bowel disease: a marker of less severe disease. Dig Dis Sci. 21 Kohan AB, Wang F, Li X, et al. Apolipoprotein A-IV regulates 2015;60:2436–45. chylomicron metabolism–mechanism and function. Am J Physiol- 3. Causey MW, Johnson EK, Miller S, et al. The impact of obe- Gastrointest Liver Physiol. 2012;302(6):G628–36. sity on outcomes following major surgery for Crohn’s disease: 22. Sun Z, Larson IA, Ordovas JM, et al. Effects of age, gender, and An American college of surgeons national surgical qual- lifestyle factors on plasma apolipoprotein A-IV concentrations. ity improvement program assessment. Dis Colon Rectum. Atherosclerosis. 2000;151:381–8. 2011;54:1488–95. 23. Martins E, Urbano J, Leite S, et al. Cardiac amyloidosis asso- 4. Aminian A, Andalib A, Ver MR, et al. Outcomes of bariatric sur- ciated with apolipoprotein A-IV deposition diagnosed by mass gery in patients with inflammatory bowel disease. OBES SURG. spectrometry-based proteomic analysis. Eur J Case Rep Intern 2016;26:1186–90. Med. 2019;6(12):001237. 5. Angrisani L, Santonicola A, Iovino P, et  al. IFSO worldwide 24. Dasari S, Amin MS, Kurtin PJ, et al. Clinical, biopsy, and mass survey 2016: Primary, endoluminal, and revisional procedures. spectrometry characteristics of renal apolipoprotein A-IV amyloi- OBES SURG. 2018;28:3783–94. dosis. Kidney Int. 2016;90:658–64. 6. Aelfers S, Janssen IMC, Aarts EO, et al. Inflammatory bowel dis- 25. Canetti D, Nocerino P, Rendell NB, et al. Clinical ApoA-IV amy- ease is not a contraindication for bariatric surgery. OBES SURG. loid is associated with fibrillogenic signal sequence. J Pathol. 2018;28:1681–7. 2021;255:311–8. 7. Wallhuss A, Ottosson J, Cao Y, et  al. Outcomes of bariat- 26. Buxbaum JN, Dispenzieri A, Eisenberg DS, et  al. Amyloid ric surgery for patients with prevalent inflammatory bowel nomenclature 2022: update, novel proteins, and recommendations disease: a nationwide registry-based cohort study. Surgery. by the International Society of Amyloidosis (ISA) Nomenclature 2023;174:144–51. Committee. Amyloid. 2022;29:213–9. Obesity Surgery 27. Sethi S, Theis JD, Shiller SM, et  al. Medullary amyloidosis 32. Yeung KTD, Penney N, Ashrafian L, et al. Does sleeve gastrec- associated with apolipoprotein A-IV deposition. Kidney Int. tomy expose the distal esophagus to severe reflux?: A systematic 2012;81:201–6. review and meta-analysis. Ann Surg. 2020;271:257–65. 28. Bois MC, Dasari S, Mills JR, et al. Apolipoprotein A-IV–associ- 33. Mabeza RM, Vadlakonda A, Chervu N, et al. Short-term outcomes ated cardiac amyloidosis. J Am Coll Cardiol. 2017;69:2248–9. of bariatric surgery in patients with inflammatory bowel disease: 29. Genco A, Castagneto-Gissey L, Gualtieri L, et al. GORD and a national analysis. Surg Obes Relat Dis. 2024;20:146–52. Barrett’s oesophagus after bariatric procedures: multicentre pro- 34. Harper JW, Zisman TL. Interaction of obesity and inflammatory spective study. Br J Surg. 2021;108:1498–505. bowel disease. WJG. 2016;22:7868. 30. Thaher O, Wollenhaupt F, Croner RS, et al. Evaluation of the 35. Singh S, Dulai PS, Zarrinpar A, et al. Obesity in IBD: epidemiol- effect of sleeve gastrectomy versus Roux-en-Y gastric bypass in ogy, pathogenesis, disease course and treatment outcomes. Nat patients with morbid obesity: multicenter comparative study. Lan- Rev Gastroenterol Hepatol. 2017;14:110–21. genbecks Arch Surg. 2024;409:156. 31. Tack J, Deloose E. Complications of bariatric surgery: dumping syndrome, reflux and vitamin deficiencies. 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Small Bowel Perforation in Roux-en-Y Gastric Bypass (RYGB) Secondary to Apolipoprotein A-IV (AApoA-IV) Type Amyloidosis

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Abstract

Background ApoA‐IV amyloidosis is a rare disease that involves the deposition of ApoA-IV protein aggregates in tissues. It commonly presents as cardiac or renal disease, but can, in rare cases, cause small bowel perforation. Methods This study describes a case of ApoA-IV type amyloidosis causing small bowel perforation after conversion of a sleeve gastrectomy (SG) into a RYGB in a Crohn’s disease (CD) and rheumatoid arthritis (RA) patient. It also considers the indications for bariatric and anti-reflux surgery in the setting of co-morbid inflammatory bowel disease (IBD), gastro- oesophageal reflux disease (GORD), and obesity. Results Obesity can reduce the efficacy of IBD medications and drives a pro-inflammatory state that may worsen IBD, however IBD patients present an operative challenge due to risk of more intestinal adhesions, potential intolerance to intestinal bypass, and risk of affecting options for future bowel resections if required. SG is often chosen over RYGB for CD patients due to limited short-term complications. However, when considering co-morbid GORD, the long-term risk of medication resistant GORD, erosive oesophagitis, and Barrett’s oesophagus with SG is significant, especially given that SG is an irreversible procedure. Conclusion There is growing evidence that bariatric surgery in IBD patients is both safe and effective, however the decision to perform bariatric surgery in an IBD patient involves consideration of the intricate interplay between obesity and IBD. Keywords Amyloidosis · Crohn's Disease · Ulcerative Colitis · Inflammatory Bowel Disease · Bariatric Surgery Background Amyloidosis is a heterogenous group of diseases involving abnormal protein deposition. Though rare, one must consider Key Points amyloidosis as a potential cause of small bowel perforation • This study describes a rare case of ApoA-IV type amyloidosis causing small bowel perforation. in patients with IBD. There is an increasing prevalence of • Bariatric surgery in IBD patients is both safe and effective. obesity among IBD patients, estimated at approximately • The decision to perform bariatric surgery in an IBD patient 15–30%, as well as a growing number of bariatric operations involves consideration of the intricate interplay between co- being performed [1–5]. Bariatric surgery is increasingly morbid obesity and IBD. • SG is often chosen over RYGB in the setting of CD, but being offered to patients with co-morbid obesity and IBD, the long-term risk of medication resistant GORD, erosive due to mounting evidence of its safety and efficacy in this oesophagitis, and Barrett’s oesophagus (BE) with SG must be cohort [4, 6–11]. Though bearing significant potential ben- considered. efit, the decision to perform bariatric surgery in IBD patients * Mona Zhi Ling Mai Jiang is a balance of multiple factors. This study describes a rare [email protected] case of apolipoprotein A-IV (AApoA-IV) type amyloidosis Stefaan De Clercq causing small bowel perforation post-RYGB and examines [email protected] the considerations involved when choosing to perform bari- atric surgery on an IBD patient. St Vincent’s Hospital, Melbourne, Australia Friendly Society Private Hospital, Bundaberg, Australia Vol.:(0123456789) Obesity Surgery Case Presentation A woman in her 50s presented approximately 2 years post-SG with a hiatal hernia and severe mixed acid and biliopancre- atic reflux. Her symptoms, including progressively worsen- ing nausea, burping, and burning epigastric pain, not con- trolled by proton pump inhibitors and anti-emetics, resulted in extremely poor quality of life. Her past medical history was significant for CD, first diagnosed in 2022 and managed with adalimumab, as well as RA, diagnosed approximately in the 1980s and managed with methotrexate and non-steroidal anti- inflammatories. Other medical history included GORD, iron deficiency anaemia, laparoscopic cholecystectomy, caesarean section, and previous bilateral total hip replacements with multiple revisions for a delayed diagnosis of hip dysplasia. SG was initially chosen in order to prevent short-term, medication-associated complications related to RYGB, as was commonly suggested in the literature at that time. How- ever, recent literature demonstrates that complication rates after various weight loss surgeries are comparable between IBD and non-IBD patients (see ‘Discussion’ for further details). Given the absence of a fundus, a hiatal hernia repair with fundoplication was not possible. Therefore, a decision was made to convert her SG to a RYGB. The preoperative screening upper and lower endoscopies demonstrated a 4 cm mixed hiatal hernia, bilious fluid in the stomach, gastritis, Fig. 1 Intraoperative images from conversion of SG to RYGB. A mild diverticulosis, and some small hyperplastic colonic pol- Hiatal hernia. B Distal RYGB anastomosis yps. Coeliac disease, disaccharidase deficiency, endocrine disorders, Helicobacter pylori infection, and psychological a transition point near the distal anastomotic site. She was admit- contraindications were excluded pre-operatively. Adali- ted to hospital with a presumed diagnosis of adhesional small mumab was discontinued perioperatively. bowel obstruction and returned to theatre for laparoscopic adhe- Intraoperatively, a 3.5 m common limb was designed, as siolysis and revision of the distal anastomosis. Intra-operatively, opposed to the usual 3 m, to accommodate a possible future a limited, contained small bowel perforation was noted at the resection of the terminal ileum (see Fig.  1). The periop- distal anastomosis, with surrounding dense adhesions. The ini- erative course of this conversion was unremarkable, and a tial distal anastomosis was resected and sent for histopathology, short segment of resected small bowel, from in between the with a new distal anastomosis formed via jejuno-jejunostomy two anastomoses, was confirmed to be viable with no histo - (see Fig. 2). Her post-operative recovery was unremarkable, and logical abnormalities. The patient was discharged on day 3 she was discharged on day 5 after the revision operation. post-operatively and was progressing well on review in the On histopathological analysis, the small bowel mucosa surgical clinic, 1 week post-operatively. showed a site of perforation and was otherwise macroscopi- She represented to the emergency department 15 days post- cally unremarkable. Microscopically, the resected margins operatively, with progressively worsening epigastric and left- were viable. There was congophilia of the small arteries and sided colicky abdominal pain, nausea and vomiting. Her tem- arterioles of the submucosa, with apple green birefringence perature was 36.4 °C, and her observations were within normal on polarisation of the slide (Congo red stain). There was limits. She had epigastric and left upper quadrant tenderness on metachromasia on crystal violet stain (see Fig.  3). These palpation, without signs of guarding, rigidity, or peritonism. She microscopic changes were consistent with amyloidosis, and had a neutrophilia of 11.65 × 10⁹/L with a total white cell count further amyloid subtyping via liquid chromatography–mass of 14.3 × 10⁹/L. There was an associated elevated platelet count spectrometry favoured AApoAIV type amyloidosis. of 460 × 10⁹/L and elevated C-reactive protein of 44 mg/L. Her She was reviewed in the surgical clinic 2 weeks after the routine blood biochemistry was otherwise unremarkable. revision operation and was recovering well. She had fol- Computed tomography (CT) abdomen and pelvis showed low-up in the amyloidosis clinic, with no evidence of the distension of jejunal bowel loops in the left upper quadrant, with Obesity Surgery more common cardiac or renal amyloid complications on screening investigations. On phone review 16 months after the revision operation, she described minimal reflux-related symptoms; she was able to return to her usual work and per- sonal duties, but continues to have persistent fatigue. Discussion Amyloidosis comprises a group of heterogeneous diseases, involving deposition of protein aggregates in various tissues [12]. It is subdivided by type according to the pathogenic fibril precursor protein [13]. Reactive or serum amyloid A protein (AA) amyloidosis is a common form of amyloidosis and occurs secondary to elevated serum amyloid A protein, which is seen in chronic inflammatory states [14]. Its syn- thesis in hepatocytes is regulated primarily by IL-1 and IL-6, with SAA levels increasing in response to inflammation and remaining elevated until the inflammation resolves [13]. In this case, our patient had CD and RA, both of which can cause AA amyloidosis, although notably, this was not the amyloidogenic protein in question. Systemic AA amyloido- sis secondary to IBD has an estimated prevalence of 0.53% and occurs more commonly in CD than ulcerative colitis (UC) [13, 15, 16]. This may be explained by the more pro- nounced acute phase response seen in CD, which may be Fig. 2 Intraoperative images from revision of RYGB, with resection related to its higher prevalence of suppurative features [13]. of contained perforation and formation of jejunojejunostomy. A Dis- tal RYGB anastomosis. B Exposed small bowel perforation Additionally, surgical resection can act as definitive man - agement for UC, leading to improved long-term control of systemic inflammation, whereas the same is not possible in CD [13]. However, systemic AA amyloidosis in the setting of IBD commonly presents as renal and cardiac disease, as opposed to gastrointestinally [17]. Fig. 3 A representative section of small bowel wall, showing green birefringence on polarisa- tion (Congo red), consistent with amyloidosis Obesity Surgery AA amyloidosis can be treated through control of the BMI [29]. SG can also be performed in patients where intesti- underlying inflammatory process. A case study by Prayman nal bypass is a relative contraindication, such as those on anti- et al. noted renal impairment or proteinuria in all included inflammatory medications or patients with IBD [29]. However, patients, with an association between poorly controlled IBD, SG is irreversible and is less effective than RYGB for sustained raised inflammatory markers, and progressive renal impair - weight loss and remission of obesity-associated comorbidities ment [13]. Consequently, reduced inflammation and lowered [29, 30]. Additionally, the effect of SGs on GORD is variable; production of SAA can also lead to amyloid resorption via some studies show improvement in GORD, likely secondary macrophage-related activity, although the exact mechanism to weight loss and reduced gastric acid secretion, while oth- is unclear [13]. In this case, the patient was on adalimumab, ers indicate worsening GORD or de novo GORD post-SG [29, which was ceased pre-operatively. Adalimumab is a human- 31]. A meta-analysis by Yeung et al. has estimated rates of de ised immunoglobulin  G1 monoclonal antibody directed novo GORD post-SG at 23%, oesophagitis at 28%, and Barrett’s against tumour necrosis factor-alpha (anti-TNF-alpha) [18]. oesophagus (BE) at 6% [32]. A prospective randomised study A study by Kuroda et al. showed a reduction in gastroduode- by Genco et al. demonstrated that the cumulative incidence of nal AA amyloid deposits upon successful treatment with anti- oesophagitis post-SG was up to 74.7% 5 years post-operative, TNF-alpha therapy, in patients with rheumatoid arthritis [19]. often with associated biliopancreatic reflux, generating BE with However, this was not the amyloidogenic protein found here. an incidence of 8% [29]. Severe medication-resistant GORD is This case demonstrated gastrointestinal ApoA-IV type amy- the most common indication for revision surgery post-SG [32]. loidosis, a rare and under-investigated form of amyloidosis. Additionally, SG eliminates the possibility of fundoplication ApoA-IV is a 46kD protein that is secreted from the small should severe GORD occur post-operatively. Therefore, RYGB bowel in response to lipid absorption and chylomicron forma- is still commonly considered the gold standard for management tion; however, its specific biological role has yet to be identified of co-morbid obesity and GORD [31]. [20, 21]. It may have antioxidant, anti-inflammatory and athero- The decision to perform bariatric and anti-reflux sur - protective functions [22]. Plasma levels of ApoA-IV increase gery in IBD patients is a complex one, taking into account with age; however, it is unclear if high levels of ApoA-IV leads the risk of operative complications, the risks of long-term to ApoA-IV amyloidosis [23, 24]. Analysis of patients attending GORD, and the benefit of weight loss on both general health the UK NHS National Amyloidosis Centre revealed 15 cases of as well as the clinical course of IBD. There is evidence that ApoA‐IV amyloidosis, with only a singular case of duodenal bariatric surgery is both safe and effective in IBD patients, ApoA‐IV amyloidosis [25]. The Mayo Clinic’s review of their with numerous studies showing no difference in weight loss, mass spectrometry database indicated that 0.45% of all 9673 quality of life, or postoperative complications between IBD cases of amyloidosis from all organs were ApoA‐IV amyloi- and non-IBD cohorts [6, 7, 9–11, 33]. Some studies noted dosis [24]. In our search of the literature, no other documented some variations on subgroup analysis. A systematic review cases of jejunal ApoA‐IV amyloidosis were found. ApoA‐IV by Aziz et al. found that post-operative bleeding and wound amyloidosis is typically systemic, with renal and cardiac mani- infections occurred at higher rates in IBD patients [10]. In a festations being the most common [26]. Renal findings include cohort study by Wallhuss et al., higher rates of postoperative progressively declining renal function with minimal proteinu- complication were noted in RYGB patients with UC, and ria [24]. Renal biopsies showed amyloid deposits in the renal higher re-admission rates were noted among CD patients; medulla for all cases, with some cases also having peritubular weight loss was found to be marginally better with RYGB amyloid deposits; the renal cortex was spared, and there was in IBD patients [7]. Additionally, in the setting of comorbid no interstitial inflammation [24, 27]. Cardiac manifestations of IBD and obesity, successful weight loss has been associ- ApoA‐IV amyloidosis included left ventricular outflow tract ated with fewer IBD-related complications [8]. This may obstruction and coronary artery disease [28]. Histopathologi- be related to the reduced efficacy of IBD medications in the cal samples of cardiac tissue showed obstructive microvascular setting of obesity [34, 35]. A case series by Aminian et al. amyloidosis in all cases and nodular interstitial deposition in noted improvement in IBD symptoms in 9 of 10 patients post some cases [28]. Unlike other forms of amyloidosis, ApoA‐IV weight loss due to bariatric surgery [4]. This may be due to amyloidosis has no specific treatments [24]. the pro-inflammatory nature of obesity, with over-expression In this case study, SG was the initially chosen bariatric pro- of IL-6, TNF-alpha, and adipokines in visceral and mesen- cedure, however the patient developed medication resistant teric fat [4]. It follows that weight loss may reduce the pro- GORD, necessitating conversion to RYGB. SG is the most com- duction of obesity-related pro-inflammatory cytokines and monly performed bariatric surgery [5]. It is especially favoured therefore reduce IBD disease activity [4]. A meta-analysis due to the short operative time and relative technical simplic- by Garg et al. noted that only 11% of patients had increasing ity, which is advantageous in patients with significant respira- IBD medication requirements post-bariatric surgery, with tory or cardiovascular comorbidities, or those with extensive the majority experiencing no change, and 46% experiencing adhesions or a restricted operative field due to extremely high a reduction in IBD medication [9]. Obesity Surgery Author Contribution M.J. wrote the main manuscript text and pre- 8. Braga Neto MB, Gregory MH, Ramos GP, et al. Impact of bariat- pared Figs. 1–3. S.D. conceptualised the study and contributed data. ric surgery on the long-term disease course of inflammatory bowel All authors reviewed the manuscript. disease. Inflamm Bowel Dis. 2020;26:1089–97. 9. Garg R, Mohan BP, Ponnada S, et al. Safety and efficacy of bari- Funding Open access funding provided by St Vincent’s Hospital Mel- atric surgery in inflammatory bowel disease patients: a systematic bourne, Victorian Health Libraries Consortium (VHLC). review and meta-analysis. OBES SURG. 2020;30:3872–83. 10. Aziz M, Haghbin H, Sharma S, et al. Safety of bariatric surgery Data Availability No datasets were generated or analysed during the in patients with inflammatory bowel disease: a systematic review current study. and amet -sisyaaln . Clin Obes. 2020;10:e12405. 11. Hudson JL, Barnes EL, Herfarth HH, et al. Bariatric surgery is a safe and effective option for patients with inflammatory bowel Declarations diseases: a case series and systematic review of the literature. Inflamm Intest Dis. 2018;3:173–9. Ethics Approval and Consent to Participate All procedures performed 12. Bustamante JG, Zaidi SRH. Amyloidosis. StatPearls [Internet]. in this study were in accordance with the ethical standards of the insti- Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 tutional ethics committee and with the 1964 Helsinki declaration and Feb 04]. Available from: http:// www. ncbi. nlm. nih. gov/ books/ its later amendments. Informed consent was obtained from the study NBK47 0285/. participant. 13. Sattianayagam PT, Gillmore JD, Pinney JH, et  al. Inflamma- tory bowel disease and systemic AA amyloidosis. Dig Dis Sci. Competing Interest The authors declare no competing interests. 2013;58:1689–97. 14. Dahiya DS, Kichloo A, Singh J, et al. Gastrointestinal amyloido- Open Access This article is licensed under a Creative Commons Attri- sis: A focused review. WJGE. 2021;13:1–12. bution 4.0 International License, which permits use, sharing, adapta- 15 Tosca Cuquerella J, Bosca-Watts MM, Anton Ausejo R, et al. tion, distribution and reproduction in any medium or format, as long Amyloidosis in inflammatory bowel disease: a systematic review as you give appropriate credit to the original author(s) and the source, of epidemiology, clinical features, and treatment. J Crohn’s Coli- provide a link to the Creative Commons licence, and indicate if changes tis. 2016;10(10):1245–53. were made. The images or other third party material in this article are 16. Hamamoto Y, Kido K, Kawamura M, et al. Subclinical amyloid included in the article’s Creative Commons licence, unless indicated deposition in inflammatory bowel diseases: a two hospital study. otherwise in a credit line to the material. If material is not included in Pathol - Res Pract. 2024;264:155682. the article’s Creative Commons licence and your intended use is not 17. Gill VS, Boddu SP, Abujbarah S, et al. Secondary amyloidosis in permitted by statutory regulation or exceeds the permitted use, you will inflammatory bowel disease patients: findings from three tertiary need to obtain permission directly from the copyright holder. To view a medical centers. Clin J Gastroenterol. 2024;17:844–53. copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 18. Fikri-Benbrahim O, Rivera-Hernández F, Martínez-Calero A, et al. Treatment with adalimumab in amyloidosis secondary to rheumatoid arthritis: two case reports. Nefrologia. 2013;33:404–9. 19. Kuroda T, Wada Y, Kobayashi D, et  al. Effective anti-TNF-α therapy can induce rapid resolution and sustained decrease References of gastroduodenal mucosal amyloid deposits in reactive amy- loidosis associated with rheumatoid arthritis. J Rheumatol. 1. Steed H, Walsh S, Reynolds N. A brief report of the epidemiol- 2009;36:2409–15. ogy of obesity in the inflammatory bowel disease population of 20. Elshourbagy NA, Walker DW, Paik YK, et  al. Structure and Tayside. Scotland Obes Facts. 2009;2:370–2. expression of the human apolipoprotein A-IV gene. J Biol Chem. 2. Flores A, Burstein E, Cipher DJ, et  al. Obesity in inflamma- 1987;262:7973–81. tory bowel disease: a marker of less severe disease. Dig Dis Sci. 21 Kohan AB, Wang F, Li X, et al. Apolipoprotein A-IV regulates 2015;60:2436–45. chylomicron metabolism–mechanism and function. Am J Physiol- 3. Causey MW, Johnson EK, Miller S, et al. The impact of obe- Gastrointest Liver Physiol. 2012;302(6):G628–36. sity on outcomes following major surgery for Crohn’s disease: 22. Sun Z, Larson IA, Ordovas JM, et al. Effects of age, gender, and An American college of surgeons national surgical qual- lifestyle factors on plasma apolipoprotein A-IV concentrations. ity improvement program assessment. Dis Colon Rectum. Atherosclerosis. 2000;151:381–8. 2011;54:1488–95. 23. Martins E, Urbano J, Leite S, et al. Cardiac amyloidosis asso- 4. Aminian A, Andalib A, Ver MR, et al. Outcomes of bariatric sur- ciated with apolipoprotein A-IV deposition diagnosed by mass gery in patients with inflammatory bowel disease. OBES SURG. spectrometry-based proteomic analysis. Eur J Case Rep Intern 2016;26:1186–90. Med. 2019;6(12):001237. 5. Angrisani L, Santonicola A, Iovino P, et  al. IFSO worldwide 24. Dasari S, Amin MS, Kurtin PJ, et al. Clinical, biopsy, and mass survey 2016: Primary, endoluminal, and revisional procedures. spectrometry characteristics of renal apolipoprotein A-IV amyloi- OBES SURG. 2018;28:3783–94. dosis. Kidney Int. 2016;90:658–64. 6. Aelfers S, Janssen IMC, Aarts EO, et al. Inflammatory bowel dis- 25. Canetti D, Nocerino P, Rendell NB, et al. Clinical ApoA-IV amy- ease is not a contraindication for bariatric surgery. OBES SURG. loid is associated with fibrillogenic signal sequence. J Pathol. 2018;28:1681–7. 2021;255:311–8. 7. Wallhuss A, Ottosson J, Cao Y, et  al. Outcomes of bariat- 26. Buxbaum JN, Dispenzieri A, Eisenberg DS, et  al. Amyloid ric surgery for patients with prevalent inflammatory bowel nomenclature 2022: update, novel proteins, and recommendations disease: a nationwide registry-based cohort study. Surgery. by the International Society of Amyloidosis (ISA) Nomenclature 2023;174:144–51. Committee. Amyloid. 2022;29:213–9. Obesity Surgery 27. Sethi S, Theis JD, Shiller SM, et  al. Medullary amyloidosis 32. Yeung KTD, Penney N, Ashrafian L, et al. Does sleeve gastrec- associated with apolipoprotein A-IV deposition. Kidney Int. tomy expose the distal esophagus to severe reflux?: A systematic 2012;81:201–6. review and meta-analysis. Ann Surg. 2020;271:257–65. 28. Bois MC, Dasari S, Mills JR, et al. Apolipoprotein A-IV–associ- 33. Mabeza RM, Vadlakonda A, Chervu N, et al. Short-term outcomes ated cardiac amyloidosis. J Am Coll Cardiol. 2017;69:2248–9. of bariatric surgery in patients with inflammatory bowel disease: 29. Genco A, Castagneto-Gissey L, Gualtieri L, et al. GORD and a national analysis. Surg Obes Relat Dis. 2024;20:146–52. Barrett’s oesophagus after bariatric procedures: multicentre pro- 34. Harper JW, Zisman TL. Interaction of obesity and inflammatory spective study. Br J Surg. 2021;108:1498–505. bowel disease. WJG. 2016;22:7868. 30. Thaher O, Wollenhaupt F, Croner RS, et al. Evaluation of the 35. Singh S, Dulai PS, Zarrinpar A, et al. Obesity in IBD: epidemiol- effect of sleeve gastrectomy versus Roux-en-Y gastric bypass in ogy, pathogenesis, disease course and treatment outcomes. Nat patients with morbid obesity: multicenter comparative study. Lan- Rev Gastroenterol Hepatol. 2017;14:110–21. genbecks Arch Surg. 2024;409:156. 31. Tack J, Deloose E. Complications of bariatric surgery: dumping syndrome, reflux and vitamin deficiencies. 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Journal

Obesity Surgery – Springer Journals

Published: May 1, 2025

Keywords: Amyloidosis; Crohn's Disease; Ulcerative Colitis; Inflammatory Bowel Disease; Bariatric Surgery

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