Introduction

Collagenous colitis (CC) and lymphocytic colitis (LC), the two main subtypes of microscopic colitis (MC), are chronic inflammatory diseases of the colon of unknown etiology. Colonic barrier dysfunction has been identified in patients with MC. However, whether molecular and structural alterations underlie an aberrant barrier in MC remains to be defined.

Aims & Methods

To identify the molecular pathways involved in the colonic epithelial brush border structure and its ultrastructural alterations in MC. Total RNA and protein were obtained from sigmoid mucosal biopsies of healthy controls (Hc) (N=11), patients with active diarrhoea predominant irritable bowel syndrome (IBS-D) patients (N=13), and active newly diagnosed naive of treatment MC patients (N=12 CC and N=12 LC). Transcriptomic and proteomic analyses were performed by RNAseq analysis and liquid chromatography mass spectrometry, respectively. Additionally, in a subset of patients (N=8 CC, N=8 LC, N=8 IBS-D and N=8 Hc) sigmoid biospies were collected and processed for scanning and transmission electron microscopy (SEM and TEM, respectively), to perform a qualitative and quantitative assessment of the colonic epithelium. Integrated data assessment was performed to explore biological and molecular functions.

Results

By RNA-Seq enrichment study, three microvilli-related pathways (organization, regulation of microvilli organization and length) were significantly enriched in the colonic mucosa of CC patients compared to LC, IBS-D and Hc. The integrated multi-omic analysis identified 28 genes with a significant positive correlation between RNA expression and its corresponding protein expression, (4 genes with a strong correlation (r>0.7, p<0.05) and 21 genes with a moderate correlation (0.3<r<0.7, p<0.05)), which were related to each other at the network level by string database analysis. Reduced expression of the microvilli proteins, was observed in CC compared to Hc, IBS-D and LC patients. Reduced expression of the actin-binding proteins, was also observed in CC. Moreover, decreased protein expression and an increased expression of proteins in the actin-membrane junction, were observed in CC and LC. Ultrastructural observation revealed that microvilli on the colonic surface of MC patients were more scattered, irregular and shorter in MC than IBS-D and Hc. Furthermore, the number of microvilli per colonocyte length (microvilli/um) was lower in CC (3.7[2.8-5.3], p<0.0001) and LC patients (5.2[4.0-6.6], p=0.01) compared to Hc (7.5[6.6-8.7]). Similarly, microvilli length was also reduced in CC (0.5[0.4-0.8], p=0.0003) and LC (0.6[0.4-1.1], p=0.04) patients compared to Hc (1.1[1.0-1.4]). No differences in the number and length of microvilli were observed between IBS-D and Hc groups.

Conclusion

Dysregulated brush border molecular pathways underlie epithelial colonic dysfunction in MC compared to Hc and IBS-D patients at both molecular and ultrastructural levels. These previously undescribed data open new perspectives in defining the pathophysiological mechanisms of MC, especially in CC. Given the fundamental role of the brush border in maintaining intestinal homeostasis and even water absorption, further understanding of these mechanisms may have significant diagnostic and therapeutic implications for MC.

Disclosure

Dr Javier Santos has served as consultant for Noventure SL, Devintecpharma, Reckitt, Ipsen, Aboca & Pileje and discloses present and past recent scientific collaborations with Salvat, Norgine, Alfa-Sigma, Cosmo, Adare, Ordesa and Danone that do not constitute a conflict of interest in developing the content of the present manuscript.

Introduction

Collagenous colitis (CC) is a form of microscopic colitis (MC), the others being lymphocytic colitis (LC), incomplete CC and incomplete LC (1). It is an inflammatory disease of the large bowel that causes chronic watery diarrhoea, abdominal pain, faecal incontinence, nightly defecation, and weight loss, resulting in significantly impaired quality of life (2). Incidence of MC has increased significantly during the past decades in some countries and the main reason for this increase is thought to be an enhanced disease recognition (3). The diagnosis of MC is challenging as it can only be diagnosed upon histological examination of colonic biopsies taken from normal or near normal appearing mucosa (1). Histological interpretation of biopsies involves subjective evaluation leading to inter-rater variability discrepancies in diagnosis and treatment plan. Deep learning-based assistance system can objectivise diagnostic key feature selection leading to minimisation of inter-rater variability and improvement of diagnostic accuracy.

Aims & Methods

The aim of this pilot study was to develop an algorithm for robust segmentation of light microscopy images of histological specimen slides (tissue slides) emphasizing key diagnostic features of CC.
Histological specimens were fixed with formalin, embedded in paraffin, cut into 3 µm sections, and stained with haematoxylin and eosin (H&E) for histological examination. Images were taken using OLYMPUS IX71 light microscope (x20 magnification) equipped with Q IMAGING EXI aqua camera at (1392 x 1040 pix.) resolution and 24-bit pixel encoding. Registered image pixel values were normalized in RGB colour space by histogram alignment using empty tissue-less areas using an algorithm described previously (4). Superpixel technique using Simple Linear Iterative Clustering algorithm (5) was used for initial segmentation of the images. All 1000 superpixels defined in each image were annotated by the expert, indicating ones containing thickened subepithelial collagen layer as the sought class among the others containing the rest of the tissue indicated as normal class. The feed – forward neural network (implemented in MatLab environment) was trained to classify superpixels using their normalized histogram bin-counts of the pixel values as a feature. Due to significant inequality in the data set, where the number of sought class superpixels was significantly smaller than the number of the remaining ones, the training set was formed by equalising it to the lowest class case’s value (18761). Only randomly selected cases of the bigger class were included in the training set.

Results

The proposed algorithm was tested on images from 5 treatment-naive patients with newly diagnosed CC. Patients' histological specimens were rated by an expert pathologist and 50 images were chosen (with changes characteristic of CC and without). The classification training process with extracted data set took 0.13 seconds on personal computer with an AMD Ryzen Threadripper 3970X 32-Core, 3.70 GHz processor and 128GB of RAM memory, epochs for training was set to 30 (after tests the model was not improving after 30 epochs) and data shuffling was set to every-epoch. The algorithm showed 0.807 accuracy, 0.801 sensitivity and 0.813 specificity.

Conclusion

The shown ability of deep learning algorithm to classify histology image segments can assist the diagnostic process of CC emphasizing thickened subepithelial collagen layer – the essential diagnostic feature.

References

1. Miehlke S, Guagnozzi D, Zabana Y, Tontini GE, Fiehn AMK, Wildt S, et al. European guidelines on microscopic colitis: United European Gastroenterology (UEG) and European Microscopic Colitis Group (EMCG) statements and recommendations. United European Gastroenterol J. 2020;
2. Verhaegh BPM, Münch A, Guagnozzi D, Wildt S, Cebula W, Diac AR, et al. Course of Disease in Patients with Microscopic Colitis: A European Prospective Incident Cohort Study. J Crohns Colitis. 2021;15(7):1174–83.
3. Weimers P, Ankersen DV, Lophaven S, Bonderup OK, Münch A, Løkkegaard ECL, et al. Incidence and Prevalence of Microscopic Colitis between 2001 and 2016: A Danish Nationwide Cohort Study. J Crohns Colitis. 2021;14(12):1717–23.
4. Petrolis R., Čižas P., Borutaitė V., Kriščiukaitis A. Method of fluorescence imaging for evaluation of membrane potential in cultured neurons using transmembrane voltage sensitive dye. Biomedical engineering 2011: Proceedings of International Conference. 14:16-19, 2011.

5. Achanta R, Shaji A, Smith K, Lucchi A, Fua P, Susstrunk S. SLIC Superpixels Compared to State-of-the-art Superpixel Methods. IEEE Transactions on Pattern Analysis and Machine Intelligence, Volume 34, Issue 11, pp. 2274-2282, May 2012

Introduction

Anastomotic leakage after foregut surgeries are often difficult to manage. The conventional way of endoscopic treatment is endoscopic stenting (ES). However, it carries a risk of stent migration and erosion. Endoscopic vacuum therapy (EVT) has recently been proposed as an alternative way of treating these leaks. EVT has the benefit of providing negative suction and promotion of granulation tissue¹. However, an exchange every 3-7 days has been suggested.

Aims & Methods

The aim of this study was to compare the treatment outcomes between ES, EVT and the combination of both. This was a retrospective multi-centre cohort study from 3 major centres in Hong Kong that performs esophagectomy and gastrectomy. All patients with anastomotic leak after total gastrectomy and esophagectomy and who were treated with ES or EVT between Jul 2008 and Apr 2023 from the Prince of Wales Hospital, Queen Mary Hospital and United Chistian Hospital were included. Patients’ demographics, type of surgery, size of anastomotic defect, treatment success rate, complications, number of procedures, duration to healing were recorded and compared. Continuous data are compared with Mann-Whitney test and categorical data are compared with Chi-square/ Fisher's exact test.

Results

A total of 63 patients were recruited (ES: 49; EVT 14. The outcomes of the study are listed in Table 1. The mean (S.D.) of defect was 15.4 (16.0)mm in the ES group and 17.8 (14.1)mm in the EVT group (p=0.39). in the EVT group, there are 3/14 patients who had failed EVT therapy and converted to ES. The success rate of each arm as a single arm therapy were similar (29/49(59.2%) in the ES group vs 6/14(42.9%) in the EVT group; p=0.28). However, there were less complications in the EVT group (2/14 (14.3%) in ES group vs. 23/49(46.9%) in EVT group; p=0.03). On the other hand, the EVT group required more endoscopic procedures (median (range) 3 1-137) procedures in the ES group vs 6(2-16) in the EVT group ; p 0.002). The days required for the anastomosis to heal were also similar (ES (61.7 (38.4) vs EVT 45.3 (25.8); p=0.37). When comparing patients treated as a single-arm therapy (ES or ET) to combination therapy (ES + EVT), the success rates has a trend towards favouring combination treatment (p=0.07).

Conclusion

Both EVT and ES are feasible and safe in treating anastomotic leaks after foregut surgeries. Although more procedures are required, EVT achieved similar success rate while having less complications when compared to ES a single arm. The use of combination therapy as compared to single-arm endoscopic therapy may achieve a higher treatment success rate.

References

1. Chan SM, Auyeung KKY, Lam SF, Chiu PWY, Teoh AYB. Current status in endoscopic management of upper gastrointestinal perforations, leaks and fistulas. Dig Endosc. 2022 Jan;34(1):43-62. doi: 10.1111/den.14061. Epub 2021 Jul 19. PMID: 34115407.

Disclosure

There is no COI.

Clinical Case Summary

A 43-year-old woman with a rectal 90mm granular laterally spreading tumor involving 50% of the circumference (distal limit at 12cm from the anal verge) underwent endoscopic submucosal dissection (ESD). Due to submucosal fibrosis, deep laceration of the muscularis propria occurred at the end of the procedure and two through-the-scope (TTS) clips were applied and broad-spectrum antibiotics were administered. In the following day, the patient developed sepsis and an emergency CT scan revealed free air in mesorectum and densification of the perirectal/presacral adipose tissues with contrast extravasation. Proctosigmoidoscopy showed an orifice of approximately 12mm, near the previous TTS clips, that communicated with a 15mm abscessed cavity, compatible with delayed perforation (Figure 1). Endoluminal vacuum therapy (EVT) was initiated with a 2cm Endo-SPONGE^® (B.Braun Medical B.V., Melsungen, Germany), partially intraluminal, without immediate complications (Figure 2). The patient was kept under parenteral nutritional, antibiotics and twice weekly EVT sponge replacement, with a total of four substitutions. The evolution was favorable with sepsis resolution, decrease of the cavity length and complete tissue granulation (Figure 3). The patient was discharged after 16 days and remained asymptomatic with complete closure at the 1.5 months follow up (Figure 4).

References

(Figure 1). (Figure 2). (Figure 3) (Figure 4).

Introduction

The Updated Sydney System recommends reporting the severity of both glandular atrophy (GA) and intestinal metaplasia (IM) as two independent parameters. However, the OLGA system assesses both GA and IM together as part of the same entity which should be reported as an average severity. The OLGIM system is based on the IM severity recommended by the updated Sydney system. Thus, the final OLGIM score can be estimated by any clinician. Currently, no system addresses the severity of both GA and IM as they are reported following the updated Sydney recommendation.

Aims & Methods

This study aimed to assess the utility of a new system, OLGIMA (Operative Link on Gastric IM and GA assessment), as a tool to identify patients at higher risk for GC in daily practice.
Consecutive diagnostic UGI endoscopies performed for any indications in patients older than 18 years old were recorded prospectively in 21 Spanish hospitals between April 2021 and July 2023. Protocolized gastric biopsies were taken according to the Updated Sydney consensus. We excluded patients with dysplasia, any malignancy, suspicion of autoimmune chronic atrophic gastritis, and lack of histological data. The severity of both GA and IM was assessed in the antrum (including incisura) and corpus following the updated Sydney system. After that, we considered the most advanced severity (none:0; mild:1; moderate:2; marked:3) provided for any of them in each of the two topographical areas. Then, the OLGIMA staging was done according to the same methodology used by the OLGA and OLGIM systems.

Results

A total of 998 patients were included. The median age was 57 (IQR 46 - 67), and 64% were women. Hp infection was identified in 334 (35%) patients (19% active infection and 16% eradicated). GA was identified in 192 (19.2%) patients which was limited to the antrum in 113 (11.3%) cases and extensive in 79 (7.9%). IM was identified in 159 (15.9%) patients which was limited to the antrum in 114 (11.4%) cases and extensive in 45 (4.5%). According to IM severity, 27 (2.7%) patients were OLGIM III/IV. According to GA severity, 22 (2.2%) patients were significantly extensive. The OLGIM system would have missed 12 (1.2%) patients with GA at higher risk. Considering both criteria, we would have detected 39 (3.9%) patients at higher risk in total (17 OLGIM III-IV, 12 extensive significative GA, and 10 both OLGIM III-IV and extensive significative GA). The new OLGIMA system categorized all 39 (3.9%) patients, OLGIM III-IV and significantly extensive GA, in the high-risk group (OLGIMA III/IV).

Conclusion

The new OLGIMA system (based on the severity of IM and GA recommended by the updated Sydney system) was able to detect patients at higher risk including all cases of OLGIM III/IV and also with advanced GA. The OLGIMA staging is much simpler and it can be estimated by any clinician regardless of whether the biopsy from incisura was taken.

References

Rugge M, Meggio A, Pennelli G et al. Gastritis staging in clinical practice: the OLGA staging system. Gut. 2007;56:631-6
Capelle LG, de Vries AC, Haringsma J et al. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71:1150-8
Pimentel-Nunes P, Libânio D, Marcos-Pinto R et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy. 2019;51:365-388.

Introduction

Treatment targets of ulcerative colitis (UC) have evolved to include not only endoscopic but also histologic remission. However, the concept of histological activity is still in its early days. We aimed to capture the attitudes towards UC histology and the uptake of standardized reporting of endoscopy and histology of UC in daily practice.

Aims & Methods

We conducted a cross-sectional survey of physicians involved in the care of IBD worldwide. The survey included 21 questions divided into 3 sections. The first recorded demographics, specialty, and level of experience of participants; the second covered clinical practices and attitudes towards the use and reporting of endoscopy, and the third of histology.

Results

Participants: In total 359 physicians, from 60 countries (54.4% Europe, 24.4% Asia, 12.9% South America, 3.7% North America, 3.2% Africa, and 1.4% Oceania) responded; 87% were gastroenterologists, the remainder other specialists involved in the care of IBD. The majority practiced in academic hospitals (54.5%) or tertiary centers (22.1%), and only around one-fifth worked in secondary hospitals (12.8%) or local practices (8.1%).
Endoscopy: When performing endoscopy in quiescent UC, 72.1% of respondents reported taking biopsies also to assess microscopic activity, while 16.8% only for dysplasia detection, and 10.4% just in case of suspicious lesions; the average number of biopsies was 10.8 (SD 7.34, range 0 to 36). In the case of active UC, the percentage of operators collecting biopsies increased to 93.6%.
Endoscopy reports included a validated score in 91.9% of cases. Mayo was nearly always used (90%), with a large difference from the second most common score UCEIS (26.5%); other indices accounted for 1.7%. Of note, except for 1 respondent, all scores different from Mayo were used in addition to, and not instead of, Mayo. When restricting the analysis to participants working in high-volume centers (>500 UC patients cared for per year) all but one (117/118) reported using the Mayo score to grade endoscopic activity, and 32% (38/117) used also other scores in addition to Mayo, mainly UCEIS.
Histology: Centers represented in the survey were roughly equally split between those with a pathologist dedicated to IBD (46.2%) and those without (51%). UC histology was used by nearly all respondents (90.5%) for initial diagnosis, 72% to monitor disease course, 62.4% to determine microscopic extension, 59.9% to confirm deep remission when considering stopping treatment, and 42.3% to increase/optimize treatment. Nevertheless, 77.2% of participants reported that standard histological indices were not routinely available, although 21.7% of these used scores in selected cases, such as clinical trials or research. Among those who used (or worked in a center that used) standard scores (160/357) the choice of which index was mixed: 64.4% (103/160) used the Nancy index, followed by Geboes 31.9% (51/160), and Robarts 20.6% (33/160), a minority applied other scores.
The majority of respondents welcomed as useful or very useful an artificial intelligence system to automate scoring of endoscopy (69%) or histology (73%).

Conclusion

UC histology reports are less standard than endoscopy ones. Most physicians consider histological activity useful when managing UC and would welcome artificial intelligence systems to automate endoscopic and histological scoring.

Disclosure

OMN has served as a speaker for Janssen, Ferring, Takeda, Pfizer, Fresenius Kabi
MI has received research grants and equipment loans from Pentax USA, Olympus, and Fujifilm; is partially funded by NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham.
LPB reports personal fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Inotrem, Al-lergan, MSD, Roche, Arena, Gilead, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSE Immunotherapeutics, Enthera, Theravance, Pandion Therapeutics, Gossamer Bio, Viatris, Thermo Fisher; grants from Abbvie, MSD, Takeda, Fresenius Kabi; stock options: CTMA.
SG has served as consultant, Steering committee member, Advisory Board Member and Drug Monitoring committee member for Janssen, Pfizer, Takeda, Abbvie, BMS, Gilead, Galapagos, Celltrion, Eli Lilly, Ferring.
SD has served as a speaker, consultant and advisory board member for Schering Plough, Abbott (AbbVie) Laboratories, Merck and Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alfa Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Vifor and Johnson and Johnson.

Remaining authors declare no relevant conflict of interest.

Introduction

Since the report of Shaker in 1994, transnasal esophagogastroduodenoscopy (T-EGDS) has been reported worldwide as one technique to facilitate comfortable procedures avoiding sedation. From 1996 in our Centre, we routinely use this technique in all the patients for diagnostic and selected operative EGDS. This approach is also suitable for the placement of percutaneous endoscopy gastrostomy (PEG) but in the published papers it has been performed only when conventional upper gastrointestinal endoscopy was unusable (dysphagic patients with neurological disease or with stenosis and/or occlusion of the mouth or pharynx). On the contrary, since 2000 we have routinely used the transnasal approach for all patients requiring PEG, reserving the oral technique when the transnasal access route is impossible.

Aims & Methods

We performed a retrospective analysis of all patients who underwent PEG placement between January 2000 and March 2023 in the Unit of Gastroenterology of San Camillo De Lellis Hospital, Rieti, Italy, in order to demonstrate the feasibility and safety of T-PEG placement in routine practice. We used ultrathin gastroscope through a nostril after assessment and lubrification, and the pull technique was used for tube placement.

Results

PEG placement was required for 256 consecutive patients (male 49.4%; female 51.6%), the average age was 79 years, within a range from 26 to 104 years. Transnasal approach was used in 162 patients (nasal group: 63.3%) while oral approach was used in 94 (oral group: 36.7%). The failure of transnasal approach was related to impossibility of nasal intubation due to narrow nasal passages or to inability to transilluminate the stomach. In these cases we needed transoral route. 14 patients underwent transoral PEG placement due to unavailability of transnasal gastroscope. The duration of the procedures was similar in both approaches (12 ±3 minutes oral vs 13±4 minutes nasal).
The most common indications for PEG insertion were neurologic disorders (n=132, 51.6 %), cerebrovascular accident (n=73, 28.5 %), esophageal cancer or head and neck cancer (n=18, 7 %), other pathologies (n=33, 12.9 %). 167 procedures were performed without sedation: 77.8 % ( n= 130) in the nasal group and only 22.1% (n=37) in the oral group. Outpatient regimen PEG placement was also significantly higher in trans nasal group (79 % vs 58 % oral group). We registered 3 major complications, 1 in oral group and 2 in nasal group (one necessitated surgery). No procedure-related death was registered. There were no unplanned re-admissions of outpatients discharged from the gastroenterology unit for procedure-related complications.

Conclusion

The more than twenty years’ experience of our center demonstrates that the transnasal approach is safety, feasible and could be routinely used in daily endoscopic practice for PEG placement. The minimally invasive technique therefore reserves sedation to a few selected cases to reduce costs, improve logistic organization and avoid anesthesia related complications.

References

1. Campo R, Montserrat A, Brullet E. Transnasal gastroscopy compared to conventional gastroscopy: a randomized study of feasibility, safety, and tolerance. Endoscopy. 1998 Jun;30(5):448-52.
2. Schuldt AL, Kirsten H, Tuennemann J, Heindl M, van Bommel F, Feisthammel J, Hollenbach M, Hoffmeister A. Necessity of transnasal gastroscopy in routine diagnostics: a patient-centred requirement analysis. BMJ Open Gastroenterol. 2019 Apr 14;6(1):e000264.
3. Dumortier J, Lapalus MG, Pereira A, Lagarrigue JP, Chavaillon A, Ponchon T. Unsedated transnasal PEG placement. Gastrointest Endosc. 2004 Jan;59(1):54-7.
4. Dumortier J, Napoleon B, Hedelius F, Pellissier PE, Leprince E, Pujol B, Ponchon T. Unsedated transnasal EGD in daily practice: results with 1100 consecutive patients. Gastrointest Endosc. 2003 Feb;57(2):198-204
5. Preiss C, Charton JP, Schumacher B, Neuhaus H. A randomized trial of unsedated transnasal small-caliber esophagogastroduodenoscopy (EGD) versus peroral small-caliber EGD versus conventional EGD. Endoscopy. 2003 Aug;35(8):641-6.