Introduction

Pancreatic ductal adenocarcinoma (PDAC) is characterized by intense fibrosis which enhances the tumor growth and drives an epithelial-mesenchymal transition. The consequence is the uncontrolled proliferation of cancer cells, including pancreatic cancer stem cells (PCSC), which may enhance the metastatic potential.

Aims & Methods

The aim of this study is to assess the prognosis of CD44, CD24 and EpCAM expression, on pancreatic endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) specimens.
A total of 35 patients diagnosed with PDAC after EUS-FNB within the Research Center of Gastroenterology and Hepatology of Craiova, were included in the study, and the samples were sent for immunohistochemical assessment. A total of three passes were performed on every PDAC tumor, to harvest enough tissue for analysis. Anti-Human CD 24 (policlonal, Abcam, ab 199140) and EpCAm (Epr 20532-225, Rb monoclonal, Abcam, ab 223582) and Human CD 44 (clone DF 1485, Agilent Tehnologies Denmark, cod M7082) were used. The slides were incubated with primary antibodies for 30 minutes at room temperature. Immunolabeling in the study group was considered positive if more than 10% of tumor cells showed a present signal and negative if less than 10% of tumor cells were immunolabeled. The intensity of immunolabeling in positive cases was assessed as weak (1), moderate (2), and intensely positive (3).

Results

We assessed a total of 300 fields and 54 (18%) were assessed as triple positive, however when all three were positive no correlations were found. The expression of CD44+ ⁄ CD24+ expression was significantly correlated with poorer outcomes (P = 0.05), whereas CD44+ ⁄EpCAM+, CD24+ ⁄EpCAM+, CD44+, CD24+, or Ep-CAM+ expression did not correlate with patient’s evolution. Among the patient characteristics, T stage and N stage were significantly correlated with poorer prognosis. CD44 and CD24 were significantly correlated with poor differentiation and high proliferation which might suggest their association with cancer aggressiveness, whereas EpCAM was correlated with well differentiation and low proliferation. When comparing patients with metastasis at the time of diagnosis, CD44+ ⁄ CD24+ expression was more intense when M1 was present (p<0.005), suggesting their prognostic role. Survival analysis showed there was no correlation with the PCSC staining.

Conclusion

EUS-FNB PSCS with CD44 + /CD24+ testing might be considered for PDAC assessment as their positivity might be correlated with a poorer outcome. They might be considered for prognosis purposes at the time of diagnosis as EUS-FNB might provide significant tissue for analysis, thus suggesting their possible therapeutic value in a clinical setting.

Disclosure

No conflicts of interest

Introduction

Guselkumab (GUS), interleukin-23p19 subunit inhibitor, has been approved for moderately to severely active Crohn’s disease (CD) in Japan. CNTO1959CRD3003 is a Phase 3, open-label, multicenter study designed to evaluate the safety and efficacy of GUS in Japanese patients with moderately to severely active CD. We report the efficacy of GUS on small bowel lesions.

Aims & Methods

The primary objective was to evaluate safety, and the secondary objective was to evaluate the efficacy of GUS at week 48 (W48). An exploratory objective was to assess the efficacy of GUS for small bowel lesions, evaluated using retrograde balloon-assisted enteroscopy (BAE). Eligible patients in this study were patients with active ileocolonic CD or small bowel CD, as clarified by endoscopic evaluation. GUS 200 mg was administered intravenously on Weeks 0, 4, and 8 and subcutaneously every 4 weeks from week12 until W44. As optional, small bowel lesions were assessed using modified simple Endoscopic Score for Crohn’s Disease [mSES-CD], excluding stricture evaluation. The sum of the proximal ileum (10-300 cm from ileocecal valve) and terminal ileum sub-scores was defined as a partial modified SES-CD (pmSES-CD). Within patients with pmSES-CD score of 4 or more at baseline, those with a score reduction of 50% at W48 from the baseline were defined as endoscopic responder; a pmSES-CD score of less than 4 points was defined as ulcer-free, and a pmSES-CD score of 0 was defined as complete mucosal healing.

Results

A total of 38 patients were enrolled and received GUS treatment. Most participants were male (24/38; 63.2%), and the median age was 40.5 (range: 20-69) years. This group included 8 with ileal type, 9 with colonic type, and 21 with ileocolonic type. The median duration of CD was 7.97 (0.4–33.0) years. Overall, 33/38 patients (86.8%) experienced an adverse event (AE) and 3/38 (7.9%) experienced a serious AE. There were no CD-related hospitalizations or surgeries, and no new safety concerns were identified regarding GUS treatment through W48.
Among the 38 patients, 15 patients were evaluated for small bowel lesion using retrograde BAE, defined as the small bowel (SB) group. Among these, the median age was 41.0 (24-69) years, and the median duration of CD was 2.92 (0.4-16.9) years. The median pmSES-CD was 8.0 (0-14) at baseline and 5.0 (0-13) at W48. 7/15 patients (46.7%) were endoscopic responders, 4/15 patients achieved ulcer-free (26.7%), and 2/15 patients (13.3%) achieved complete mucosal healing at W48 (Table.1). Three participants (20.0%) showed improvement of 5 points or more in the lesions of the proximal ileum as measured by pmSES-CD. Two of three ileal type patients achieved ulcer-free at W48. No AE of strictures were reported through W48.

Table 1. Result of efficacy of guselkumab treatment on small bowel lesions.

Conclusion

Overall, this study showed that GUS is well-tolerated and effective for treating patients with moderately to severely active CD, and the results also suggested the effectiveness of GUS in small bowel lesions.

Disclosure

TH: Grant: EA pharma Co. Ltd., AbbVie GK, Pfizer Inc., Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co. Ltd., JIMRO Co.Ltd, Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Zeria Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Kissei Pharmaceutical, Boston Scientific
Consulting fees: EA pharma Co. Ltd.,AbbVie GK,Pfizer Inc.,Mitsubishi Tanabe Pharma Corporation,Takeda Pharmaceutical Co. Ltd.,Gilead Sciences, Inc.,Eli Lilly and Co.,Janssen Pharmaceutical K.K.,Bristol Myers Squibb,Abivax
Payment or honoraria for lectures, presentations, speakers;
EA pharma Co. Ltd.,AbbVie GK,Pfizer Inc.,Mitsubishi Tanabe Pharma Corporation,Kyorin Pharmaceutical Co. Ltd.,JIMRO Co.Ltd,Mochida Pharmaceutical Co., Ltd.,Takeda Pharmaceutical Co. Ltd.,Zeria Pharmaceutical Co. Ltd.,Nippon Kayaku Co. Ltd.,Janssen Pharmaceutical K.K.
TK: Grant: Abbie GK, Alfresa Pharma Corporation, EA Pharma, Gilead Sciences, Inc. Nippon Kayaku Co., Ltd., Eli Lilly Japan K.K., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Pfizer Japan Inc., Sekisui Medical, Takeda Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation, Zeria Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Consulting fees :Takeda Pharmaceutical Co., Ltd., Alfresa Pharma Corporation, Zeria Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Abbie GK, Pfizer Japan Inc., Janssen Pharmaceutical K.K., JIMRO Co., Ltd., Galapagos, Takeda Pharmaceutical Co., Ltd., Expert testimony : EA Pharma Co., Ltd., KISSEI Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc., Nippon Kayaku Co., Ltd., Alfresa Pharma Corporation, Abbie GK, Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K.
KW: Consulting fees: EA Pharma Co., Ltd., Payment or honoraria for lectures, presentations, speakers: Takeda Pharmaceutical Co., Ltd., AbbVie Japan Co., Ltd., EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., JIMRO Co., Ltd.
Participation on a Data Safety Monitoring Board or Advisory Board: Takeda Pharmaceutical Co., Ltd., Leadership or fiduciary role in other board, society, committee : Japanese Society of Gastroenterology, Japanese Society of Gastrointestinal Endoscopy, Japanese Gastroenterological Association, Japan Society of Coloproctology, Japanese Society of Mucosal Immunology, Japan Society for Inflammatory Bowel Disease, Japanese Society of Small Intestinal Disease, Japanese Association for Capsule Endoscopy, Research group of intractable IBD, the Ministry of Health, Labor and Welfare in Japan
KO All support for the present manuscript : J&J Innovative Medicine, Payment or honoraria for lectures, presentations, speakers: AbbVie Inc, EA Pharma Co.,Ltd, Janssen Pharmaceutical, KYORIN Pharmaceutical, Mitsubishi Tanabe Pharma, MOCHIDA PHARMACEUTICAL, Nippon Kayaku Co.,Ltd, OLYMPUS CORPORATION, Takeda Pharmaceuticals, Zeria Pharmaceutical Co., Ltd.
ME: Grant: Kyorin Pharmaceutical Co. Ltd, Payment or honoraria for lectures, presentations, speakers: AbbVie GK, Mitsubishi Tanabe Pharma, EA Pharma Co., Ltd, Janssen Pharmaceutical, Takeda Pharmaceuticals, Pfizer Japan Inc., Gilead Sciences Inc., Mochida Pharmaceutical Co. Ltd
TO: Payment or honoraria for lectures, presentations, speakers: AbbVie GK., Takeda Pharmaceutical Co. Ltd., and KISSEI Co. Ltd
NH: Expert testimony : J&J Innovative Medicine
TM: None
TS, KM, MC, HH and SY are employees of Johnson & Johnson.

Introduction

Primary thromboprophylaxis is used in the post-partum and the post-surgical period. 2014 Canadian Association of Gastroenterology guidelines and a 2021 Nature Reviews consensus recommend outpatient thromboprophylaxis only for those ambulatory inflammatory bowel disease (IBD) patients at high risk of thromboembolic events.

Aims & Methods

We aimed to analyse our inpatient burden and our rate of post-discharge thromboembolic (TEEs) in those with primary and secondary diagnoses pertaining to IBD. We also aimed to identify associated risk factors.
Our hospital inpatient and radiology databases were queried for discharges with primary and secondary diagnoses pertaining to IBD and scans pertaining to TEEs respectively.

Results

1,601 discharges pertaining to 954 individual patients were identified over the 13-years ended 2024. 54% (n=870) were female. Median age was 44 (IQR:32-59). 58% (n=932) pertained to Crohn’s disease.
Investigations for TEEs were performed during 117 admissions (7.3%). 10 patients had inpatient TEEs (0.6%). Age ≥ 50 years was significantly associated with inpatient TEE (Odds ratio [OR]: 1.89; 95% confidence intervals [CI]: 1.13-3.16; p=0.01). Male gender (OR: 0.92; 95% CI: 0.59-1.44; p=0.72), ulcerative colitis subtype (OR: 1.51; 95% CI: 0.95-2.41; p=0.08) and inpatient surgical intervention (OR: 1.39; 95% CIs: 0.89-2.17; p=0.15) were not significant associated factors.
63 discharges (3.9%) had imaging querying TEEs performed within 180 days. Six patients (0.4%) had TEEs within this time frame. No significant associations were identified for age ≥50 years (OR: 1.16; 95% CIs: 0.68-1.99; p=0.59), male gender (OR: 0.84; 95% CIs: 0.48-2.17; p=1.47, p=0.55), ulcerative colitis subtype (OR: 1.12; 95% CIs: 0.65-1.91; p=0.68), inpatient surgical intervention (OR: 1.37; 95% CIs: 0.79-2.35; p=0.26) or prior VTE (OR not calculable) in relation to post-discharge TEEs.

Conclusion

Our incidences of inpatient and post-discharge TEEs were low over 13-years. In agreement with international guidelines, we recommend against the need for routine primary prophylaxis in the post-discharge ambulatory period.

References

1. Nguyen GC, Bernstein CN, Bitton A, et al. Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology. Gastroenterology. 2014;146(3):835-848.e6. doi:10.1053/j.gastro.2014.01.042
2. Olivera PA, Zuily S, Kotze PG, et al. International consensus on the prevention of venous and arterial thrombotic events in patients with inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18(12):857-873. doi:10.1038/s41575-021-00492-8

Introduction

Intestinal ultrasound (IUS) is a non-invasive method that is increasingly used to monitor disease activity in patients with inflammatory bowel disease.¹ There is currently no consensus on the appropriate implementation of IUS to assess post-surgical recurrence in Crohn’s disease (CD). ​

Aims & Methods

The aim of this study was to determine appropriate parameters for evaluating postoperative recurrence of CD using IUS after surgery. The modified RAND-University of California Los Angeles appropriateness method (RAM)² was implemented using an international panel of 16 experts, including gastroenterologists, surgeons, radiologists, and methodologists, to evaluate the appropriateness of statements related to using IUS for assessing postoperative recurrence of CD. This exercise specifically focused on assessing the anastomosis, neoterminal ileum after ileocecal resection, and primary anastomosis in CD. To inform statement generation for the RAM, a systematic review was performed to identify parameters described in the literature for the sonographic evaluation of postoperative disease recurrence in patients with CD. Statements were developed focusing on when, where, and how sonographic parameters should be assessed after surgery. Panellists voted anonymously in 2 rounds of surveys containing up to 122 statements, rating each statement for appropriateness on a 9-point Likert scale (1=highly inappropriate; 5=uncertain; 9=highly appropriate). Median appropriateness ratings were summarised, and interquartile ranges were calculated. The statement list and survey results were discussed in moderated videoconferences prior to voting. The panellists met in person to discuss the results and ratify the final statements.

Results

After 2 rounds of voting, 80% of the statements were rated as appropriate with agreement. IUS findings in the neoterminal ileum and the inlet of the neoterminal ileum were considered likely to reflect clinically meaningful disease. Recognising that immediate postoperative changes related to surgical healing may mimic CD, IUS should not be performed within 4 weeks of resection in the context of evaluating postoperative recurrence. Defining the entire component of the anastomosis as consisting of colonic blind side, ileal blind side, neoterminal inlet, and neoterminal ileum, if any were visible/present, was considered appropriate by the panellists. However, there was uncertainty with describing and measuring thickening within the blind loops and whether those segments represent postoperative recurrence. Use of bowel wall thickness, bowel wall stratification, bowel wall vascularity on Doppler, mesenteric inflammatory fat, lymphadenopathy, submucosal layer thickness, muscularis propria layer thickness, small bowel peristalsis, free fluid, abscess, inflammatory mass, fistula/sinus tract, anastomotic or neoterminal ileal stricture, luminal narrowing, pre-stenotic dilation, and stricture length were considered appropriate to assess postoperative CD recurrence, and parameters for each component were identified.

Conclusion

This first set of internationally guided recommendations (Table) for using IUS to assess postoperative recurrence of CD has been developed to facilitate standardisation of a non-invasive method of monitoring patients following surgical bowel resection.

References

¹ Dolinger MT, Kayal M. Intestinal ultrasound as a non-invasive tool to monitor inflammatory bowel disease activity and guide clinical decision making. World J Gastroenterol. 2023;29(15):2272-2282. Doi: 10.3748/wjg.v29.i15.2272
² Fitch K, Bernstein SJ, Aguilar MD, et al. The RAND/UCLA Appropriateness Method User’s Manual. Santa Monica, CA: RAND Corporation, 2001.

Disclosure

KLN has received consulting fees from AbbVie, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Pendopharm, Pfizer, and Takeda, with speaker's fees from AbbVie, Fresenius Kabi, Janssen, Pfizer and Takeda; and research support from Pfizer, and the Helmsley Trust.
SA has received speaker/honoraria fees from AbbVie, Fresenius Kabi, Janssen, Pfizer, and Takeda; and received research grants from A.I Vali and ATGen.
MA received consulting fee from Nikkiso Europe, Mundipharma, Janssen, AbbVie, Ferring, Galapagos, Alfasigma, Lilly, Sandoz, and Pfizer.
AdBvO has received speaker fees from Amgen, Takeda, and Janssen Pharmaceuticals.
PGK is a speaker and consultant for AbbVie, Celltrion, Johnson & Johnson, Pfizer and Takeda. He received scientific grants from Pfizer and Takeda, and is involved in clinical research for Ventyx, Roche, and Takeda.
CL has received advisory/consulting fees from AbbVie, Agomab, Celltrion, JnJ, Lilly, Pfizer, Takeda, Fresenius Kabi, Pendopharm, and Ferring.
CM received lecture and/or consulting fee from AbbVie, Alfasigma, Biocon Biologics, Bristol Myers Squibb, Ferring, Galapagos, Gilead, Lilly, J&J, Pfizer, and Takeda.
GM has received lectures or consulting fees from AbbVie, Janssen, Samsung, Galapagos, and Fresenius-Kabi.
RP reports being a Consultant for Abbott, AbbVie, Abbivax, Alimentiv Inc. (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB; reports Speaker’s Fees for: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; and reports Advisory Boards for: AbbVie, Alimentiv Inc. (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.
MR reports receiving consulting/advisory fees from AbbVie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, and Roche.
JR has received lectures fees from AbbVie and Takeda; is or has been advisor for Gilead, Takeda, Agomab, Janssen, Boehringer Ingelheim, Lumen, Ferring, and Bracco; and has received consultant fees from Alimentiv Inc. He received scientific grants from Takeda and AbbVie.
AS has received consulting fees from Stryker and Johnson and Johnson.
SAT reports grant support from Takeda; consultancy with AstraZeneca; and shareholder of Motilent.
RW reports speaker or consultancy fees by Alimentiv Inc, Pfizer, Takeda, J&J, and Nautilus Scientific.
WAB reports no competing interests.
NKC reports being a Consultant for Samsung and Speaker for Bristol-Myers Squibb.
KBG has received grants from AbbVie, Pfizer Inc., Celltrion and Galapagos; consultancy fees from AbbVie, Eli Lilly, Galapagos, Gilead, Janssen Pharmaceuticals, Pfizer Inc., Samsung Bioepis, and Takeda; and speaker’s honoraria from AbbVie, Celltrion, Eli Lilly, Ferring, Janssen Pharmaceuticals, Pfizer Inc, Takeda, and Tillotts.
SA, SK, and LJC are employees of Alimentiv Inc.
CM has received consulting fees from AbbVie, Alimentiv Inc., Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, and Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv Inc., Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, and Takeda; royalties from Springer Publishing; and research support from AbbVie, Ferring, and Pfizer.

Introduction

Total retocolectomy with ileal pouch anal anastomosis (IPAA) is the surgical procedure of choice for patients with ulcerative colitis (UC) refractory to clinical treatment and familial adenomatous polyposis (FAP) with many polyps in the rectum. Primary ileitis of the ileal pouch (IP) is one of the most common complications in UC, being rare in FAP. Previous studies have identified an increase in pro-inflammatory cytokines, as well as alterations in the apoptosis and macroautophagy pathways markers in the IP mucosa of UC patients, compared to those with FAP and normal distal ileum (controls). Since autophagy and apoptosis can be modulated by endoplasmic reticulum (ER) stress, we investigated this pathway in IP of UC compared to PAF and controls.

Aims & Methods

The aim was to evaluate the modulation of ER stress in the IP mucosa of UC and FAP patients who underwent IPAA, compared to controls. Thirty-two patients were included, ten in the UC group, twelve in FAP group and ten in the control group. Patients who had undergone ileostomy closure for less than one year and had clinical, histological, or endoscopic evidence of pouchitis were excluded. The patients underwent routine colonoscopy, and biopsies were performed from the IP. For the control group, biopsies were taken from the normal distal ileum. The local Ethics Committee approved the study. The biopsies were processed for RNA extraction and subsequent gene expression analysis using the quantitative PCR (qPCR) technique. The following transcripts were investigated: IRE1 (ERN), PERK (EIF2AK3), ATF6, GRP78 (HSPA5), GRP94 (HSP90B1), ATF3, STC2, DDIT3, DNAJC3, and CALR. Nonparametric tests were used for statistical analysis, with a significance level of p<0.05.

Results

The pouchitis disease activity index (PDAI) was applied to verify the absence of pouchitis, with all patients scoring lower than 7. There was no increase in the transcriptional level of the main ER stress pathway markers (ERE1, PERK, and ATF6) in the IP without pouchitis. However, there was a significantly lower expression of DDIT3 in the UC and FAP groups compared to the control (p≤0.05), which may suggest a deficiency in counterbalance the ER stress activation. On the other hand, concerning the UPR pathway markers, the levels of CALR and HSP90B1 were significantly higher in the IP of UC compared to the respective IP afferent loop (p≤0.05), supporting potential activation of the ER stress in the IP in the UC group. Additionally, the transcriptional level of ATF3 was significantly higher in the PAF group compared to the control (p≤0.05), which may indicate a counter-regulatory mechanism in response to tissue damage, which was not verified in the UC group.

Conclusion

Our findings demonstrated that markers of the unfolded protein response (UPR) signaling pathway, which is activated in response to ER stress, are modulated in the IP mucosa of UC patients, even in the absence of pouchitis. These results may explain the propensity to IP inflammation in UC patients. They may guide the identification of additional molecular pathways contributing to inflammation of the IP and the search for new therapeutic targets.

References

1. Negreiros LMV, Pascoal LB, Genaro LM, et al. Pouchitis: insight into the pathogenesis and clinical aspects. Am J Transl Res. 2022 Jul 15;14(7):4406-4425.
2. Rodrigues BL, Dotti I, Pascoal LB, et al. Endoplasmic Reticulum Stress in Colonic Mucosa of Ulcerative Colitis Patients Is Mediated by PERK and IRE1 Pathway Activation. Mediators Inflamm. 2022 Feb 9;2022:6049500.
3. Paiva NM, Pascoal LB, Negreiros LMV, et al. Ileal pouch of ulcerative colitis and familial adenomatous polyposis patients exhibit modulation of autophagy markers. Sci Rep. 2018 Feb 8;8(1):2619.
4. Qiao D, Zhang Z, Zhang Y, Chen Q, Chen Y, Tang Y, et al. Regulation of Endoplasmic Reticulum Stress-Autophagy: A Potential Therapeutic Target for Ulcerative Colitis. Front Pharmacol. 2021;Volume 12-2021.

Clinical Case Summary

Background: Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome in which the symptomatology of intestinal obstruction occurs without any mechanical cause. This syndrome may reveal or complicate celiac disease during follow-up.
Cases presentation: We report two cases of 40 and 24-year-old women. The first is followed since the age of 8 for celiac disease on a poorly followed gluten-free diet and consulted for repeated pseudo-occlusive syndromes. the second was admitted to the surgery department for a recurrent occlusive syndrome which resolves after gastric aspiration, then referred to our service for exploration of chronic diarrhea. For both, no mechanical obstruction was found. Ionic disorders and lymphoma were also ruled out. The diagnostic of CIPO was retained. The intestinal mucosal biopsy was characteristic of celiac disease. The evolution was favorable under a gluten-free diet. Symptoms of CIPO never recurred.
Conclusion: Our observations highlight that CIPO may be a rare and severe complication of celiac disease, which should always be suspected since the gluten-free diet can improve symptoms and prevent recurrences.