Crypt Distortion Research Articles

Massive bleeding and perforation due to post-colectomy pan-enteritis with a significant response to biologic in a patient with ulcerative colitis: a case report

BackgroundPost-colectomy pan-enteritis in ulcerative colitis (UC) is very rare, but it is often severe and fatal. We present a case of massive bleeding and perforation due to post-colectomy pan-enteritis, which showed a significant response to biologics in a UC patient.Case presentationA 30-year-old woman with a 5-month history of pancolitis UC underwent subtotal colectomy with ileostomy and mucosal fistula for refractory UC. She was diagnosed with small bowel obstruction on postoperative day (POD) 8 and bowel bleeding was observed on POD18. Reoperation was performed for bowel obstruction and bleeding on POD20. Intraoperatively, adhesive small bowel obstruction in the ileum and multiple erosions and ulcers with perforation were observed throughout the small bowel. We diagnosed post-colectomy pan-enteritis, and jejunostomy, lavage, adhesiolysis, and a simple closure of the perforated ileum were performed. High-dose steroid therapy for pan-enteritis was administered immediately after reoperation, and infliximab was administered because of worsening bleeding on day 3 after reoperation. Bleeding decreased one day after biologic administration and bleeding completely disappeared on day 10 after biologic administration. Specimens obtained from the terminal ileum at colectomy showed a normal ileum without inflammation and villus atrophy, while specimens from the perforated ileum showed congestion, villous atrophy, epithelial erosion, and mononuclear cell infiltration. No cryptitis, crypt distortion, or basal plasmacytosis (common characteristics in UC) were observed in either specimen.ConclusionAn early diagnosis and intervention are important for post-colectomy pan-enteritis, and infliximab may be effective. Post-colectomy pan-enteritis with a multiple ulcer phenotype has different histological characteristics from UC and may have a different pathogenesis.

Bisphenol S exposure induces intestinal inflammation via altering gut microbiome

Bisphenol S (BPS), a substitute for bisphenol A, is widely used in the manufacture of food packaging materials, raising concern over its toxicity. However, evidence is still lacking on whether gut microbiota involved in BPS induced intestinal inflammation in mammals, as well as its underlying mechanism. Using mouse BPS exposure model, we found intestinal inflammation characterized by shortened colon length, crypt distortion, macrophage accumulation and increased apoptosis. As for gut microbiota, 16s rRNA gene amplicon sequencing showed BPS exposure induced gut dysbiosis, including increased pro-inflammatory microbes such as Ileibacterium, and decreased anti-inflammatory genera such as Lactobacillus, Blautia and Romboutsia. Besides, LC-MS/MS-based untargeted metabolomic analysis indicated BPS impaired both bacteria and host metabolism. Additionally, transcriptome analysis of the intestine revealed abnormal gene expression in intestinal mucosal barrier and inflammation. More importantly, treating mice with antibiotics significantly attenuated BPS-induced gut inflammation via the regulation of both bacterial and host metabolites, indicating the role of gut microbiota. Collectively, BPS exposure induces intestinal inflammation via altering gut microbiota in mouse. This study provides the possibility of madecassic acid, an anti-inflammatory metabolite, to prevent BPS-induced intestinal inflammation and also new insights in understanding host-microbiota interaction in BPS toxicity.

Lack of ATP2B1 in CD4+ T Cells Causes Colitis.

The ATP2B1 gene encodes for a calcium pump, which plays a role in removing Ca2+ from cells and maintaining intracellular Ca2+ homeostasis. Reduction of the intracellular Ca2+ concentration in CD4+ T cells is thought to reduce the severity of colitis, while elevation of Ca2+ in CD4+ T cells induces T cell hyperactivity. Our aim was to clarify the role of ATP2B1 in CD4+ T cells and in inflammatory bowel disease development. A murine CD4+ T cell-specific knockout (KO) of ATP2B1 was created using a Cre-loxP system. CD4+ T cells were isolated from thymus, spleen, and blood using fluorescence-activated cell sorting. To quantify messenger RNA levels, quantitative real-time polymerase chain reaction was performed. Although the percentages of CD4+ T cells in both KO mouse spleen and blood decreased compared with those of the control samples, both T-bet (a T helper 1 [Th1] activity marker) and GATA3 (a Th2 activity marker) expression levels were further increased in KO mouse blood CD4+ T cells (vs control blood). Diarrhea and colonic wall thickening (with mucosal changes, including crypt distortion) were seen in KO mice but not in control mice. Prior to diarrhea onset, the KO mouse colon length was already noted to be shorter, and the KO mouse stool water and lipid content were higher than that of the control mice. Tumor necrosis factor α and gp91 expressions were increased in KO mouse colon. Lack of ATP2B1 in CD4+ T cells leads to Th1 and Th2 activation, which contributes to colitis via elevation of tumor necrosis factor α and oxidative stress.

Panaxynol improves crypt and mucosal architecture, suppresses colitis-enriched microbes, and alters the immune response to mitigate colitis.

Ulcerative colitis (UC) is an idiopathic inflammatory disease of the large intestine, which impacts millions worldwide. Current interventions aimed at treating UC symptoms can have off-target effects, invoking the need for alternatives that may provide similar benefits with less unintended consequences. This study builds on our initial data, which showed that panaxynol-a novel, potent, bioavailable compound found in American ginseng-can suppress disease severity in murine colitis. Here we explore the underlying mechanisms by which panaxynol improves both chronic and acute murine colitis. Fourteen-week-old C57BL/6 female mice were either given three rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or one round to induce acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage three times per week for the study duration. Consistent with our previous findings, panaxynol significantly (P < 0.05) improved the disease activity index and endoscopic scores in both models. Using the acute model to examine potential mechanisms, we show that panaxynol significantly (P < 0.05) reduced DSS-induced crypt distortion, goblet cell loss, and mucus loss in the colon. 16S Sequencing revealed panaxynol altered microbial composition to suppress colitis-enriched genera (i.e., Enterococcus, Eubacterium, and Ruminococcus). In addition, panaxynol significantly (P < 0.05) suppressed macrophages and induced regulatory T-cells in the colonic lamina propria. The beneficial effects of panaxynol on mucosal and crypt architecture, combined with its microbial and immune-mediated effects, provide insight into the mechanisms by which panaxynol suppresses murine colitis. Overall, this data is promising for the use of panaxynol to improve colitis in the clinic.NEW & NOTEWORTHY In the current study, we report that panaxynol ameliorates chemically induced murine colitis by improving colonic crypt and mucosal architecture, suppressing colitis-enriched microbes, reducing macrophages, and promoting the differentiation of regulatory T-cells in the colonic lamina propria. This study suggests that this novel natural compound may serve as asafe and effective treatment option for colitis patients.

OP21 Spatial Transcriptomics of Pre-treatment Biopsies Revealing Molecular Maturation State and Chronic Crypt Damage, Reflecting Histological Severity, as Predictors of Primary Responsiveness to TNF-α Inhibitors in Bio-naive Ulcerative Colitis Patients

Abstract Background Biologic therapies, particularly tumor necrosis factor-alpha inhibitors (TNFi), have greatly advanced the treatment of ulcerative colitis (UC), yet significant number of patients still do not respond to these treatments. For UC management, achieving both histologic and molecular healing is crucial, highlighting the need for more comprehensive therapeutic strategies. Despite extensive research, there is a significant gap in studies that simultaneously assess histologic and molecular changes at both the crypt and lamina propria (LP) levels. Our study addresses this gap by investigating TNFi-resistant UC patients, utilizing spatial transcriptomics to discern specific cell types within histologic sections and integrating these insights to enhance understanding of UC treatment responses. Methods We evaluated 56 patients categorized into test (n=23), validation (n=31), and healthy control groups (n=2). Each underwent biopsies at the same sites before (preTx) and after treatment (postTx), as shown in Figure 1A. This study focused on a 3-month follow-up of patients who were administered TNFi as a primary biologic therapy following resistance to conventional treatments. We used digital spatial profiling to analyze gene expression in the crypt and LP, as seen in Figures 1B and 1C. We then correlated molecular data with morphological characteristics and quantitatively evaluated histologic factors, especially crypt distortion and atrophy, reported as percentages (%). Results Among the study participants, 29 were classified as responders (R) to TNFi, while 25 were non-responders (non-R). A comparative analysis of gene expression between R and non-R groups revealed a differential expression pattern: 72 genes in the crypt and 105 genes in the LP across varying histologies, as shown in Figure 1D and 1E. Notably, in the preTx samples of non-R, crypts displayed significantly lower expression of genes associated with the maturation of colonocytes, including BEST4, C10orf99, CA2, CA4, CA7, PHGR1, SLC26A2, SLC26A3, LYPD8, CLCA1, and SCNN1, compared to the R group (Figure 1F). Furthermore, when correlating spatial transcriptomic data with histomorphological features, we observed that crypt distortion and atrophy were significantly more pronounced in the non-R group than in the R group in the preTx biopsy samples (Figures 1G and 1H). Conclusion Our study's spatial profiling unveils distinct molecular and histologic features between R and non-R to TNFi among bio-naive UC patients. The evaluation of chronic histological features such as crypt distortion, and molecular maturation status, in predicting TNFi response highlights the potential of early histologic assessment in guiding biologic therapy in the UC treatment pathway.

Pharmacological effects of biologically synthesized ginsenoside CK-rich preparation (AceCK40) on the colitis symptoms in DSS-induced Caco-2 cells and C57BL mice

BackgroundDespite the notable pharmacological potential of natural ginsenosides, their industrial application is hindered by low oral bioavailability. Recent research centers on the production of less-glycosylated minor ginsenosides. PurposeThis study aimed to explore the effect of a biologically synthesized ginsenoside CK-rich minor ginsenoside complex (AceCK40), on ameliorating colitis using DSS-induced colitis models in vitro and in vivo. MethodsThe ginsenoside composition of AceCK40 was determined by HPLC-ELSD and UHPLC-MS/MS analyses. In vitro colitis model was established using dextran sodium sulfate (DSS)-induced Caco-2 intestinal epithelial model. For in vivo experiments, DSS-induced severe colitis mouse model was established. ResultsIn DSS-stimulated Caco-2 cells, AceCK40 downregulated mitogen-activated protein kinase (MAPK) activation (p < 0.05), inhibited monocyte chemoattractant protein-1 (MCP-1) production (p < 0.05), and enhanced MUC2 expression (p < 0.05), mediated via signaling pathway regulation. Daily AceCK40 administration at doses of 10 and 30 mg/kg/day was well tolerated by DSS-induced severe colitis mice. These doses led to significant alleviation of disease activity index score (> 36.0% decrease, p < 0.05), increased luminal immunoglobulin (Ig)G (> 37.6% increase, p < 0.001) and IgA (> 33.8% increase, p < 0.001), lowered interleukin (IL)-6 (> 65.7% decrease, p < 0.01) and MCP-1 (> 116.2% decrease, p < 0.05), as well as elevated serum IgA (> 51.4% increase, p < 0.001) and lowered serum IL-6 (112.3% decrease at 30 mg/kg, p < 0.001). Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining revealed that DSS-mediated thickening of the muscular externa, extensive submucosal edema, crypt distortion, and decreased mucin droplets were significantly alleviated by AceCK40 administration. Additionally, daily administration of AceCK40 led to significant recovery of colonic tight junctions damaged by DSS through the elevation in the expression of adhesion molecules, including occludin, E-cadherin, and N-cadherin. ConclusionThis study presents the initial evidence elucidating the anti-colitis effects of AceCK40 and its underlying mechanism of action through sequential in vitro and in vivo systems employing DSS stimulation. Our findings provide valuable fundamental data for the utilization of AceCK40 in the development of novel anti-colitis candidates.

The Histology-Driven Differential Diagnosis in Bowel Inflammatory Conditions Is Not All That Obvious: Evidence from a Survey Based on Digital Slides.

(1) Background: when the pathologist faces histologic slides from colonoscopies in daily practice, given the large number of entities and etiologies under inflammatory bowel conditions, in-depth definition of the histological spectrum and the recommendations of current guidelines are often not enough to conclusively define a diagnostic framework. Histological patterns should be organized hierarchically in flowcharts that consider the correlation with clinical data. We conducted an online survey asking a group of gastroenteropathologists to apply a pattern classification based on the most significant lesions in colitis differential diagnosis: crypt distortion and activity. (2) Methods: digital slides from 20 endoscopy samples were analyzed by twenty pathologists and classified according to the occurrence of crypt distortion (nondestructive-destructive colitis) and subsequently to the evidence of activity (ND1-2-3, D1-2). (3) Results: in 8 out of 20 (40%) cases, the participants reached a full agreement regarding the evaluation of crypt distortion (5 cases: nondestructive colitis; 3 cases: destructive colitis). The calculated agreement was k = 0.432. In the second-level quiz (ND1-2-3 and D1-2), full agreement between participants was achieved for 7 of the 28 (25%) possible classifications, with k = 0.229. (4) Conclusions: The findings from this survey are indicative of an unexpectedly low consensus, even among dedicated pathologists, about the recognition of histological changes that are commonly considered critical lesions in the histologic identification of bowel non-neoplastic diseases. In our opinion, these divergences imply a significant risk of misdiagnosis of bowel inflammatory conditions, hampering the usefulness of histological assessment.

Clinical, Endoscopic, and Histologic Characteristics of Patients with Solitary Rectal Ulcer Syndrome at a Tertiary Care Center

Abstract Objective Solitary rectal ulcer syndrome (SRUS) is a chronic disorder of defecation presenting with bleed per rectum, mucorrhea, tenesmus, perianal discomfort, etc. We aim to report clinical, endoscopic, and histologic features of SRUS in patients who underwent either colonoscopy or sigmoidoscopy at our center. Materials and Methods We performed retrospective analysis of all patients diagnosed with SRUS on endoscopy and confirmed by histopathologic examination at our center between January 2010 and June 2022. Data retrieved included demographic details, clinical features along with endoscopic, and histopathological findings of SRUS patients. Results The study included 132 patients with SRUS with mean (± standard deviation) age of 45 (± 20.6) years and male to female ratio of 1.5:1. While most of the patients presented with a combination of symptoms, the most common clinical presentation was bleeding per rectum (82%). Rectal ulcers, either single or multiple, were the predominant findings on endoscopy followed by polypoidal lesions. Histology showed fibromuscular obliteration and crypt distortion in all patients. Biofeedback training, lifestyle changes, and sucralfate enema were successful in about 87% of the patients at the end of 6 weeks and about 76% at the end of 12 weeks with surgery for rectal prolapse being performed in two of our patients. Conclusion SRUS presents with a myriad of symptoms and requires a high index of suspicion by the treating physician(s). While the most common presenting symptom in our study was rectal bleed rectal bleed; ulcers, either solitary or multiple, ulcers, either solitary or multiple, were the commonest endoscopy findings. Endoscopic findings along with histopathology confirm the diagnosis.

Hypusination Maintains Intestinal Homeostasis and Prevents Colitis and Carcinogenesis by Enhancing Aldehyde Detoxification

The amino acid hypusine, synthesized from the polyamine spermidine by the enzyme deoxyhypusine synthase (DHPS), is essential for the activity of eukaryotic translation initiation factor 5A (EIF5A). The role of hypusinated EIF5A (EIF5AHyp) remains unknown in intestinal homeostasis. Our aim was to investigate EIF5AHyp in the gut epithelium in inflammation and carcinogenesis. We used human colon tissue messenger RNA samples and publicly available transcriptomic datasets, tissue microarrays, and patient-derived colon organoids. Mice with intestinal epithelial-specific deletion of Dhps were investigated at baseline and in models of colitis and colon carcinogenesis. We found that patients with ulcerative colitis and Crohn's disease exhibit reduced colon levels of DHPS messenger RNA and DHPS protein and reduced levels of EIF5AHyp. Similarly, colonic organoids from colitis patients also show down-regulated DHPS expression. Mice with intestinal epithelial-specific deletion of Dhps develop spontaneous colon hyperplasia, epithelial proliferation, crypt distortion, and inflammation. Furthermore, these mice are highly susceptible to experimental colitis and show exacerbated colon tumorigenesis when treated with a carcinogen. Transcriptomic and proteomic analysis on colonic epithelial cells demonstrated that loss of hypusination induces multiple pathways related to cancer and immune response. Moreover, we found that hypusination enhances translation of numerous enzymes involved in aldehyde detoxification, including glutathione S-transferases and aldehyde dehydrogenases. Accordingly, hypusination-deficient mice exhibit increased levels of aldehyde adducts in the colon, and their treatment with a scavenger of electrophiles reduces colitis. Hypusination in intestinal epithelial cells has a key role in the prevention of colitis and colorectal cancer, and enhancement of this pathway via supplementation of spermidine could have a therapeutic impact.

Freeze-dried jaboticaba (Myrciaria jaboticaba) peel powder, a rich source of anthocyanins and phenolic acids, mitigates inflammation-driven colorectal cancer in mice

This study aimed to characterize the peel of jaboticaba (Myrciaria jaboticaba (Vell.) O. Berg) by spectrophotometry and chromatography, and investigate its effects on mice with inflammation-driven colorectal cancer (CRC). Freeze-dried jaboticaba peel (FDJP) showed a high antioxidant capacity in vitro, and to be mostly a source of cyanidin-3-O-glucoside, gallic acid, and ellagic acid. In the animal bioassay, FDJP added at 5% in the diet during 114 days completely abolished the formation of adenocarcinoma, which had an incidence of 75% in the non-treated group. Animals consuming FDJP showed low histology damage regarding inflammatory infiltrate, edema, and crypt distortion. FDJP significantly reduced the colonic levels of proinflammatory markers interleukin-1beta and cyclooxygenase-2, and demonstrated a probability to decrease the expressions of inducible nitric oxide synthase and nuclear factor kappa B. In summary, FDJP mitigated CRC, possibly by avoiding triggering inflammation. Such benefit may come from its rich content in anthocyanins and phenolic acids.

HISTOPATHOLOGICAL FEATURES IN RELAPSE OF ULCERATIVE COLITIS.

Background and objective: To determine the frequencies of various histopathological features of relapse in previously diagnosed cases of ulcerative colitis . Methods: This was a Cross sectional study conducted at Histopathology department of Sheikh Zayed hospital Lahore from 1/6/2014 to 1/12/2014. Two hundred and seventy colonic biopsies were assessed using 3% margin of error and 95% of the confidence level. Patients clinically relapsed with ulcerative colitis including both genders in age group from 11 to 80 years were included. Biopsy specimen fixed in 10% formalin were received. Processing was done and sections stained with hematoxylin and were examined by the pathologist. College of Physicians and Surgeons Pakistan gave approval for this study. Data was then analyzed and entered by the SPSS version15. Results: Total number of patients were 270,out of which all of the patients have shown chronic inflammation and increase number of neutrophils in lamina propria (100%), focal lymphoid aggregate in 162/270(60%), increased number of eosinophils in lamina propria in 108/270(40%), cryptitis in 216/270(80%), crypt distortion in 202/270(75%), mucin depletion in151/270 (56%) and crypt abscess formation in 148/270(55%). Conclusion: Hence, cryptitis and crypt abscess were observed to be most commonly occurring significant and reliable featuress of relapse in ulcerative colitis.

Solitary Rectal Ulcer Syndrome in Patients Presenting With Lower Gastrointestinal Bleeding: A Tertiary-Care Hospital Experience.

Solitary rectal ulcer syndrome (SRUS) is a benign rectal condition associated with defecation disorder that has multifactor pathologies and variable findings on presentation, endoscopy, and histopathology. A diagnostic dilemma with an overlap of differentials and step-wise management that starts with conservative therapies and goes up to repeated surgeries in case of failure of the conservative approach. This study aims to observe clinical, endoscopic, and histological features of SRUS in patients presenting with lower gastrointestinal bleeding. The study was conducted at the Department of Gastroenterology, Medical Teaching Institute, Lady Reading Hospital Peshawar from October 2018 to April 2020. After written informed consent, 257 patients (149 males and 108 females) from ages 15 to 70 who presented with lower GI bleeding were included via non-probability convenient sampling. Sociodemographic details were recorded in a pre-designed proforma. A colonoscopy was performed with the Colonoscope CF200 Z, Olympus Tokyo, Japan, and findings were noted. Suspected lesions were magnified, dyed with 0.2% indigo carmine, biopsied from the middle and edges of the ulcer, and sent for histopathology. All data were recorded and analyzed in SPSS-20. The mean with SD was calculated for quantitative variables, and frequency and percentages were calculated for qualitative variables. The chi-square test was used to check the significance, and a p-value of <0.05 was considered statistically significant. SRUS was found in 17 (6.6%) patients with lower GI bleeding, with a male predominance of 57% (n=11). Perirectal bleeding, constipation, mucous discharge, abdominal pain, and anemia were common clinical findings. Solitary lesions, ulceration, and anterior rectum location were the most common endoscopy findings. Obliterated lamina propria with collagen, ulceration, crypt distortion, and inflammatory infiltrates were common histopathological findings. SRUS is a benign defecation disorder commonly presenting with lower GI bleeding, constipation, straining, and abdominal pain. It needs a stepwise approach with conservative management, medical management, biofeedback, and surgeries as a last resort.

P361 Risk of persistent gastrointestinal inflammation after treatment with immune checkpoint inhibitors

Abstract Background Immune checkpoint inhibitors (ICI) can cause immune-mediated gastrointestinal toxicity, but the long-term persistence of this toxicity is unknown. We aimed to describe the characteristics of patients with gastrointestinal inflammation persisting more than six months after discontinuation of ICI. Methods We included consecutive patients treated between October 2010 and March 2022 for endoscopic or histological gastrointestinal inflammation persisting at least six months after the last administration of ICI. Results Among 178 patients treated for a gastrointestinal immune-mediated adverse event during ICI therapy, 14 (8%) patients had chronic lesions persisting more than 6 months after the last ICI administration. The median follow-up time was 13 months after discontinuation of ICI. The most common symptom was watery diarrhea (54%). Ten (77%) patients had colon involvement and three (21%) had ileal involvement. Ten patients (77%) had an inflammatory phenotype, while two (15%) had a penetrating and one had (8%) a stricturing phenotype. All patients had lymphoplasmacytic infiltrate and basal plasmacytosis, and s54%) had crypt distortion. Two (15%) patients underwent surgery and nine (69%) received specific treatment, including five treated with vedolizumab. Among the patients who were followed up for at least one year, endoscopic lesions persisted at 1 year after stopping ICI in 4/6 patients, and at 2 years in 3/4 patients. Conclusion Eight percent of patients who had gastrointestinal toxicity due to ICI develop chronic inflammatory bowel disease characterized by watery diarrhea, colitis and lymphoplasmacytic infiltrate.

P016 Dietary supplementation with Brazilian jaboticaba-sabará fruit (Myrciaria jaboticaba (Vell.) O. Berg) ameliorates colitis-driven colorectal cancer in mice

Abstract Background Individuals with inflammatory bowel diseases (IBD) are at a high risk of developing colorectal cancer (CRC). Recently, pre-clinical studies have demonstrated that South American crops are rich sources of bioactive compounds that can act against both IBD and CRC. Therefore, our study aimed to characterize the freeze-dried peel of jaboticaba-sabará (Myrciaria jaboticaba (Vell.) O. Berg), a native Brazilian berry, and understand its preventive effects on a mouse model of IBD-related CRC. Methods Jaboticaba peel powder was chemically characterized by its contents of polyphenols, carotenoids, and dietary fibers. For the animal experimentation, male BALB/c mice were given in their diets 0, 2.5, or 5% jaboticaba powder for 17 weeks. On day 28, animals received an injection of the carcinogenic azoxymethane. During days 35-42 and 49-56, a solution with dextran sodium sulfate was given as drinking water to mice to induce chronic colitis. Clinical parameters were checked frequently in order to compose the Disease Activity Index (DAI). On day 119, mice were euthanized, their organs were measured, and the colon was checked for visible tumors. Histology processing was performed to assess the incidence of adenocarcinomas and for a score analysis of inflammatory-related parameters. Results High-performance liquid chromatography showed that dry jaboticaba is a rich source of cyanidin-3-O-glucoside (1.45%), gallic acid (0.32%), ellagic acid (0.3%), and delphinidin-3-O-glucoside (0.1%). Other compounds were found in a lesser amount, including protocatechuic acid (0.012%), rutin (0.006%), syringic acid (0.005%), and lutein (0.002%). Additionally, the powder showed relevant contents of soluble (11.3%) and insoluble (24.9%) dietary fibers (Table 1). Animals with colitis-driven CRC had diarrhea and showed bleeding in their feces, besides an average of 11 ± 2.1 visible tumors. On the contrary, animals that received 5% jaboticaba had a significant recovery in their colon length and showed reduced signs of colitis, including less bloody diarrhea, therefore, reduced DAI. The 5% intervention decreased the number of tumors to an average of 4.2 ± 1.0 (Figure 1). Adenocarcinoma incidence went from 66.6% in the control cancer group to 37.5% in the 5% jaboticaba group, the latter in which 50% of the animals did not show any alteration (adenoma or adenocarcinoma). Finally, the 5% jaboticaba diet significantly reduced crypt distortion and the depletion of goblet cells. The 2.5% jaboticaba diet had no beneficial effects. Conclusion Our preliminary results indicate that anthocyanin- and fiber-rich jaboticaba could represent a potential prevention tool for IBD-related CRC. Further analyses are necessary to understand the molecular mechanisms of jaboticaba on CRC.

Histologic Predictors of Clinical Outcomes and Healthcare Utilization in Patients With Ileal Pouch-Anal Anastomosis.

The prognostic significance of histology in ileal pouch-anal anastomosis (IPAA) remains unclear. The aim of this study was to evaluate if histologic variables are predictive of IPAA clinical outcomes and healthcare utilization. This was a retrospective cohort study of patients with IPAA undergoing surveillance pouchoscopy at a tertiary care institution. Pouch body biopsies were reviewed by gastrointestinal pathologists, who were blinded to clinical outcomes, for histologic features of acute or chronic inflammation. Charts were reviewed for clinical outcomes including development of acute pouchitis, chronic pouchitis, biologic or small molecule initiation, hospitalizations, and surgery. Predictors of outcomes were analyzed using univariable and multivariable logistic and Cox regression. A total of 167 patients undergoing surveillance pouchoscopy were included. Polymorphonuclear leukocytes (odds ratio [OR], 1.67), ulceration and erosion (OR, 2.44), chronic inflammation (OR, 1.97), and crypt distortion (OR, 1.89) were associated with future biologic or small molecule initiation for chronic pouchitis. Loss of goblet cells was associated with development of chronic pouchitis (OR, 4.65). Pyloric gland metaplasia was associated with hospitalizations (OR, 5.24). No histologic variables were predictive of development of acute pouchitis or surgery. In an exploratory subgroup analysis of new IPAA (<1 year), loss of goblet cells was associated with acute pouchitis (OR, 14.86) and chronic pouchitis (OR, 12.56). Pyloric gland metaplasia was again associated with hospitalizations (OR, 13.99). Histologic findings may be predictive of IPAA outcomes. Pathologists should incorporate key histologic variables into pouchoscopy pathology reports. Clinicians may need to more closely monitor IPAA patients with significant histologic findings.

S6 Serrated Epithelial Change: To Follow or Not to Follow?

Case: Dysplasia surveillance is an important aspect of management in inflammatory bowel disease (IBD). A variety of lesions can be identified on surveillance biopsies, including serrated epithelial change (SEC). In this report, we aim to raise awareness about SEC and discuss its implications in IBD patients. Case 1: A 76 -year-old female with left sided ulcerative colitis (UC) on Adalimumab underwent a colonoscopy which revealed a flat 1 cm rectal polyp. Remainder of the colon was endoscopically normal and biopsies showed quiescent colitis, however polyp returned as SEC. Case 2: A 64 -year-old male with UC on Infliximab and a history of low grade dysplasia (LGD) on 2 previous surveillance colonoscopies presented for colonoscopy with chromoendoscopy. Previous area of dysplasia was biopsied and showed SEC with LGD. Remainder of colonic biopsies showed quiescent disease. Discussion: In accordance with established guidelines, patients with IBD are recommended to have regular colonoscopies every 1 to 2 years for dysplasia surveillance. Our patient in Case 2 had LGD for several years before SEC was seen, which raised the question of the importance of SEC and its dysplastic potential. While traditional serrated adenomas (TSA) and sessile serrated polyps are commonly seen in both IBD and non-IBD patients, SEC is a distinct entity that has only been described in patients with IBD. It has also been termed hyperplastic-like change and flat serrated change. There is no standardized endoscopic appearance of SEC. Histologically, SECs have crypt distortion and loss of perpendicular orientation of crypts with no typical features of dysplasia. Review of the current literature demonstrates differing opinions on the dysplasia risk associated with SEC. Brcic et al identified mutations in KRAS and BRAF genes in several serrated lesions, that were not seen in mucosa with SEC, implying that the neoplastic potential is comparatively lower in SEC. However, a separate study of serrated lesions identified evidence of aneuploidy that was present in TSA and SEC samples suggesting that there may be an association with neoplasia on a molecular level. From a clinical perspective, in 1 study of patients with SEC, 21% developed dysplasia over the observed 8-year period, suggesting a possible association between SEC and dysplasia, albeit not a causative one. A more recent case controlled study of 196 patients showed that in UC patients with SEC, the rate of metachronous/synchronous neoplasia was 26.5% compared with 3.1% in UC patients without SEC. High grade dyplasia was also seen more commonly in patients with UC and SEC (11.2%) compared with 2% in UC patients with SEC. This study concluded that due to this association, close attention should be paid on subsequent surveillance colonoscopies to patients with SEC. Conclusion: Ultimately, further controlled studies and prospective trials are needed to assess the true impact of SEC as a risk factor for dysplasia. This is still an under-recognized entity and the associations that have been noted in the recent studies suggest that closer endoscopic follow up may be necessary when SEC is revealed on surveillance biopsies.

S1891 A Diagnostic Dilemma: Primary Sclerosing Cholangitis With High IgG4 vs IgG4-Related Sclerosing Cholangitis

Introduction: Two etiologies of sclerosing cholangitis with overlapping features are Type 2 IgG4-Related Sclerosing Cholangitis (IgG4-SC) and Primary Sclerosing Cholangitis with high IgG4 (PSC). Here, we present a complex case of a young patient with features of both diseases. Case Description/Methods: A 25-year-old Caucasian female with a medical history of diabetes and no previous pancreatic disease was incidentally found to have an AST and ALT in the low 200s, total bilirubin 2.6, and alkaline phosphatase of 1130 concerning for cholestatic obstruction. She was asymptomatic and not jaundiced at the time. Subsequent MRCP revealed a dilated common bile duct. The patient underwent ERCP/EUS demonstrating a common bile duct stricture. A plastic stent was placed, and cells for cytology/FISH analysis were unyielding for malignancy. Repeat ERCP/EUS was performed a few months later for stent exchange. Biopsies to evaluate the indeterminate stricture yielded IgG4+ plasma cells up to 14/HPF. Based on the findings suspicious for IgG4-SC, she started prednisone therapy for one month. Subsequent labs demonstrated mild improvement in alkaline phosphatase to 450, total bilirubin 0.2, and a normal IgG4 level but with persistent elevation of total IgG 1.5 times the upper limit of normal. Repeat ERCP demonstrated resolution of the distal biliary stricture. She never developed abdominal pain, jaundice, weight changes or loss of appetite. Six months later, LFTs began to uptrend and a third ERCP/EUS demonstrated new distal biliary stricture. Biliary biopsies showed dense lymphoplasmacytic infiltrates and fibrosis with an average of 10 IgG4 positive plasma cells/HPF. Liver biopsies showed periductal fibrosis and a fibro-obliterative duct lesion. Given the concern for PSC, colonoscopy was performed with biopsies showing mild crypt distortion, mild eosinophilia, and rare neutrophils in the lamina propria. The patient remained asymptomatic throughout the disease course but had persistent biochemical hepatitis despite being on steroid therapy. A shared provider-patient decision was made to withhold immunosuppressive or biologic therapy. Discussion: In this case, the patient’s epidemiologic, clinical, and histological factors were more consistent with PSC. Conversely, the mild biochemical and stricture steroid-responsiveness were initially more suggestive of IgG4-SC. It is imperative to delineate between the two, as prognosis, treatment-responsiveness, and anticipated comorbidities differ.

Variation of histopathological features in colonic mucosal biopsy with clinical diagnosis of suspicious inflammatory bowel disease in Dr. Soetomo General Academic Hospital, Surabaya period 2015 - 2019

Inflammatory bowel diseases (IBDs) are chronic inflammatory diseases that often relapse and divided into two types, Crohn’s disease (CD) and ulcerative colitis (UC). Histopathological findings in colonic mucosal biopsy with clinical diagnosis suspicious IBD can vary and overlap. Therefore, criteria and guidelines have been created to improve the diagnostic accuracy. This descriptive observational study was performed retrospectively with cross sectional approach. 122 samples of colonic mucosal biopsies with clinical diagnosis of suspicious IBD were retrieved from histopathological archives in the Anatomical Pathology Laboratorium of Dr. Soetomo Hospital, Surabaya during period 1st January 2015 - 31st December 2019. The most common histopathological feature found in colonic mucosal biopsies with clinical diagnosis of suspicious IBD was crypt distortion (97/79.50% samples), and the least was irregularity of surface epithelium (30/24.59% samples). 10 of 122 samples was concordant with the final diagnosis of IBD. Knowledges regarding the variations of histopathological features in colonic mucosal biopsy specimens with clinical diagnosis of suspicious IBD, can improve the diagnostic accuracy.

Immunohistochemical detection of chlamydia trachomatis in sexually transmitted infectious proctitis

IntroductionSince 2003, a progressive increase in sexually transmitted infections (STI), presented as proctitis, has been described in homosexual men. In 2013 Arnold et al. described microscopic features that enable pathologists to formulate a histological diagnosis of STI related proctitis. The aim of this study is to identify the presence of Chlamydia trachomatis by immunohistochemistry in a group of patients with male to male sexual activity and pathology compatible with STI proctitis.MethodsCross-sectional study. The study included 54 patients with risky sexual activity and histopathology compatible with STI-proctitis according to Arnold´s recommendations. The Chlamydia trachomatis identification was carried out retrospectively on paraffin blocks using mouse monoclonal antibodies from Santa Cruz biotechnology.Resultsall patients were young men with male to male sexual activity, 69% were positive for HIV. The most common endoscopic presentation was rectal ulcer (61%). Basal lymphoplasmacytic inflammation and mild crypt distortion were the most common histological findings. The immunohistochemical study identified positivity for Chlamydia trachomatis in 40% (18 of 45 tested) of STI proctitis cases.DiscussionThe epidemiological and endoscopic characteristics of the patients studied are similar to those previously reported. In accordance with Arnold et al., the most common histological findings were (a) mild distortion of the crypts; (b) dense and basal lymphoplasmacytic infiltrate and (c) scarcity of eosinophils. The positivity of chlamydia trachomatis in immunohistochemistry was lower than others studies that used PCR for this purpose. We did not find similar published studies to compare our results.ConclusionsIn summary, 54 cases of patients with STI related proctitis are presented, all of them with distinctive histological characteristics and third of the cases tested positive by IHC for Chlamydia trachomatis.

In vivo assessment of inflammatory bowel disease in rats with ultrahigh-resolution colonoscopic OCT.

A technology capable of high-resolution, label-free imaging of subtle pathology in vivo during colonoscopy is imperative for the early detection of disease and the performance of accurate biopsies. While colonoscopic OCT has been developed to visualize colonic microstructures beyond the mucosal surface, its clinical potential remains limited by sub-optimal resolution (∼6.5 µm in tissue), inadequate imaging contrast, and a lack of high-resolution OCT criteria for lesion detection. In this study, we developed an ultrahigh-resolution (UHR) colonoscopic OCT and evaluated its ability to volumetrically visualize and identify the pathological features of inflammatory bowel disease (IBD) in a rat model. Owing to its improved resolution (∼1.7 µm in tissue) and enhanced contrast, UHR colonoscopic OCT can accurately delineate fine colonic microstructures and identify the pathophysiological characteristics of IBD in vivo. By using a quantitative optical attenuation map, UHR colonoscopic OCT is able to differentiate diseased tissue (such as crypt distortion and microabscess) from normal colonic mucosa over a large field of view in vivo. Our results suggest the clinical potential of UHR colonoscopic OCT for in vivo assessment of IBD pathology.