Clinical Case Summary

An hemoperitoneum may be the initial presentation of a liver tumour. A good differential diagnosis is critical, including trauma, vascular rupture and tumours.
A 79-year-old male, retired welder and painter, consulted for weight loss, abdominal pain and distension of 3 months of evolution. Ascitic semiology led to do a paracentesis with hematic debit. An urgent computerized tomography (CT) reported hemoperitoneum secondary to multicentric liver tumor with active bleeding (Figure 1) and intratumoral pseudoaneurysms compatible with angiosarcoma, performing an urgent transarterial embolization (Figure 2). Extension CT ruled out distant disease, magnetic resonance imaging (MRI) was realized (Figure 3) and fine needle aspiration (FNA) showed atypical cellular with CD31 expression (Figure 4), consistent with primary hepatic angiosarcoma (PHA). Given the bilobar involvement, surgery was dismissed and he was treated with chemotherapy (CTX), dying at 10 months of diagnosis.
PHA is a rare entity (2% of primary liver tumor) with an annual prevalence of 200 worldwide cases and a male predominance (3:1) at 60 years. It has been associated to exposure to vinyl chloride, arsenic or thoracotrast, but currently 75% of diagnoses have unknown aetiology.
Diagnosis is based on anatomopathology and inmunohistochemistry, including atypical cellularity in FNA and expression of vascular markers as ERG (100%), CD34 (87%) and CD31 (79%). Imaging tests are non-specific, with hypodense lesions in CT and T2-weighted hyperintense sequence in MRI.
Due to its aggressiveness, around 60% of PHA presents lymph nodes or lung, bones or spleen metastases at diagnosis. Liver resection is the only potentially curative treatment because it is a radioresistent tumour. Transplantation is not recommended due to its high recurrence rate. PHA has less than 6 months of overall survival (OS) without treatment. Otherwise, patients with CTX treatment has a OS of 3% at 2 years of diagnosis.

Introduction

The 6-minute withdrawal time for colonoscopy is widely considered the standard of care. However, there may not be appropriate if the 6-minute is equally divided into various colon segments. Since the adenoma detection in each colon segment is not the same, there may be differences with the withdrawal time in different colon segments.

Aims & Methods

Our objective was to evaluate the relationships between adenoma detection rate (ADR) and respective withdrawal time in different colon segments. Outpatients, age range 18-75 years, undertaking complete colonoscopy were enrolled in this study from November 2019 to November 2020 in the digestive endoscopy center. The entire colon was divided into four different segments: ascending colon, transverse colon, descending colon and rectosigmoid colon. The respective withdrawal time and ADR in each colon segment were recorded respectively.

Results

A total of 586 outpatients (279 males, 307 females) enrolled in this study and the general ADR was 38.2%. The positive withdrawal time (adenomas detected) was longer than negative withdrawal time (non-adenomas detected) (334.04±24.21 secs vs 303.65±5.20 secs, t=1.26, P<0.001). ADR in ascending colon, transverse colon, descending colon and rectosigmoid colon were respectively 30.5%, 2.9%, 3.1% and 7.5%. While all of their positive withdrawal time were longer than negative withdrawal time (94.34±33.76 secs vs 70.40±41.84 secs, t=3.31, P=0.001; 85.40±49.76 secs vs 71.66±36.87 secs, t=1.95, P=0.025; 80.29±39.85 secs vs 69.73±35.96 secs, t=1.40, P=0.016;100.95±55.92 secs vs 80.96±42.87 secs, t=3.61; P<0.001, respectively). The withdrawal time threshold in the ascending colon, transverse colon, descending colon, rectosigmoid colon determined by receiver operating characteristic (ROC) curve were 77s, 61s, 56s and 109s, respectively. In the ascending colon, ADR was significantly higher (47.0% vs 33.1%, P < 0 .001) when the colonoscopy withdrawal time was ≥77s. When the withdrawal time was ≥61s in the transverse colon (42.7% vs 32.7%, P = 0.013), ≥59s in the descending colon (42.3% vs 29.9%, P=0.004) and ≥109s in rectosigmoid colon (52.2% vs 33.9%, P < 0 .001), ADR was also significantly higher. After adjusting for age, sex and BMI, Logistic regression analysis showed that withdrawal time ≥ 77s in the ascending colon (OR, 1.796; 95% CI, 1.273-2.532; P < 0 .001), ≥ 61s in the transverse colon (OR, 1.535; 95% CI, 1.094-2.155; P = 0.013), ≥56s in the descending colon (OR, 1.722; 95%CI, 1.193-2.486; P =0.004) and ≥109s in the rectosigmoid colon (OR, 2.134; 95% CI, 1.446-2.350; P < 0.001) were independent risk factors for the increase of ADR.

Conclusion

ADR and withdrawal time are all various in individual colon segments. During the operation of colonoscopy, withdrawal time in the ascending colon may be shortened appropriately. The adenomas in the rectosigmoid colon are more likely to be detected and do not take longer withdrawal times. We need to choose the appropriate time according to different colon segments.

References

[1] Sung H, Ferlay J, Siegel R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 2021;71(3): 209-249.
[2] Shaukat A, Kahi C J, Burke C A, et al. ACG clinical guidelines: colorectal cancer screening 2021. Official journal of the American College of Gastroenterology ACG 2021;116(3): 458-479.
[3] Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 2021;14(10):101174.
[4] Araghi M, Soerjomataram I, Bardot A, et al. Changes in colorectal cancer incidence in seven high-income countries: a population-based study. The lancet Gastroenterology & hepatology 2019;4(7): 511-518.
[5] Siegel RL, Torre LA, Soerjomataram I, et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut 2019;68(12):2179-2185.
[6] Kaminski MF, Robertson DJ, Senore C, et al. Optimizing the Quality of Colorectal Cancer Screening Worldwide. Gastroenterology 2020;158(2):404-417.
[7] Lee JK, Jensen CD, Levin TR, et al. Long-term Risk of Colorectal Cancer and Related Deaths After a Colonoscopy With Normal Findings. JAMA Intern Med 2019;179(2):153-160.
[8] Ladabaum U, Dominitz JA, Kahi C, et al. Strategies for colorectal cancer screening. Gastroenterology 2020;158(2):418-432.

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

Endoscopic submucosal dissection (ESD) and transanal minimally invasive surgery (TAMIS) are considered standard of care minimally invasive local en bloc resection techniques for larger benign rectal polyps and early-invasive rectal cancer. To optimize post-procedural care for patients, it is important to obtain more insight in the post-procedural physical recovery of both techniques.

Aims & Methods

This is an ancillary study of the multicenter non-inferiority randomized TRIASSIC-trial (Netherlands Trial Register: NL7083) that compares the outcomes of ESD and TAMIS for large (≥20mm) rectal polyps (1). Patients were 1:1 randomized between ESD or TAMIS and monitored with a smartwatch during a 14-day baseline period prior to resection and a 28-day post-procedural recovery period. A mixed-effects model was fitted for physical activity to describe the recovery period. Recovery was defined as reaching ≥90% of the baseline step-count for 2 consecutive days. If patients did not meet this pre-defined definition of recovery within 28 days post-treatment, a recovery time of 30 days was used in the analyses. This study analyzed subjective time to recovery through an end-of-study questionnaire and post-procedural pain through a self-reported pain diary.

Results

A total of 40 patients were included (20 ESD, 20 TAMIS). The mean age was 66.7 years (SD 7.4), 57.5% was male, and median polyp size was 42.5mm (IQR 25). Histological assessment showed a benign polyp in 82.5% and early-stage T1 rectal cancer in 17.5%. Seventeen patients (85%) in the ESD group and 15 patients (75%) in the TAMIS group were physically recovered within the 28-day post-procedural recovery period (p=0.43). The median time to physical recovery was 6.5 days (IQR 18) after ESD and 14.5 days (IQR 21.3) after TAMIS (p=0.022). Subjective time to recovery was 1-2 weeks in 47.5%, 3-4 weeks in 17.5%, and 32.5% did not feel completely recovered within 28 days. There was a significant correlation (Spearman’s rho = 0.66, p<0.001) between the physical (smartwatch) and subjective (end-of-study questionnaire) time to recovery. Post-procedural pain scores in the first week were similar between ESD and TAMIS (p=0.86) and were significantly associated with patients’ level of physical activity (p<0.01); for each point increase in the pain score total step count compared to baseline decreased by 14% after both ESD (95%CI 4-22%) and TAMIS (95%CI 5-22%). Additionally, higher post-procedural pain scores were significantly associated with a prolonged time to recovery (p=0.001). Other factors that were significantly associated with a prolonged time to physical recovery were polyp diameter ≥4cm (only in the ESD group; p=0.003), polyp located ≤1cm from the dentate line, and female sex (only in the TAMIS group, p=0.02 and p=0.03, respectively)

Conclusion

ESD-treated patients have a shorter physical recovery time of ~1 week as compared to ~2 weeks for TAMIS-treated patients. Post-procedural pain is a potentially modifiable factor that significantly influences physical activity and time to physical recovery after ESD and TAMIS.

References

1. Dekkers N, Boonstra JJ, Moons LMG, Hompes R, Bastiaansen BA, Tuynman JB, et al. Transanal minimally invasive surgery (TAMIS) versus endoscopic submucosal dissection (ESD) for resection of non-pedunculated rectal lesions (TRIASSIC study): study protocol of a European multicenter randomised controlled trial. BMC Gastroenterology. 2020;20(1):225.

Disclosure

The TRIASSIC trial is funded by ZonMW (Efficiency program: 852001926) and Applied Medical. Funding bodies had no role in the study design, data collection and analyses, decision to publish, or preparation of this abstract.

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

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.