Introduction

Large non-pedunculated colorectal polyps (LNPCP's) are significant precursors of colorectal cancer, commonly treated by piecemeal endoscopic mucosal resection (pEMR). When histology reveals a focus of adenocarcinoma invading the sub-mucosa, the resection is often considered non curative and salvage surgery is performed. Recent evidence shows that the risk of residual cancer in the bowel wall or lymph nodes of the surgical specimen are uncommon and that in some cases surgery may be avoided even when a focus of invasive cancer is found in the EMR specimen.

Aims & Methods

This is a retrospective observational study aimed to evaluate the prevalence, characteristics, and outcomes of covert carcinoma in LNPCPs resected by EMR in a two academic centers.
Data was collected from a prospective cohort of LNPCPs at two academic centers in Israel. We collected patient, lesion and procedural characteristics prospectively.
EMR was performed by 3 experienced endoscopist with dedicated EMR training. Piecemeal EMR was performed after endoscopic assessment for polyps that were deemed not to have sub-mucosal invasion according to accepted classification systems. Lesions suspected to containing invasive cancer were referred to surgery without endoscopic resection were excluded from the analysis.
For lesions containing invasive carcinoma, data was collected on Kikuchi classification, presence of tumor budding and lymphovascular invasion, grade of tumor differentiation, and status of the deep margin. Surgical data included presence of residual carcinoma in the surgical specimen, grading, margin involvement, and lymph node involvement.

Results

We analyzed 546 LNPCPs referred for resection at the two centers. We identified 27 cases of covert carcinoma, accounting for 4.9% of all LNPCPS resected by piecemeal EMR. A multidisciplinary tumor board deemed resection curative in 7 cases, and 18 patients were refferd for surgical resection. One patient refused surgery, and One patient was lost to follow up.
None of the surgical specimens had lymph node metastasis. In one case residual carcinoma was found in the bowel wall of the surgical specimen. No recurrence of colorectal cancer, presence of metastasis on imaging or elevation of CEA was documented for any of the patients during follow up of two year.

Conclusion

In conclusion, our study shows that covert carcinoma is relatively rare when EMR is performed in a high-volume center by expert endoscopists. In addition, the data suggests that even in these cases, the risk of metastatic disease is probably very low.

References

1. Kudo S ei, Lambert R, Allen JI, Fujii H, Fujii T, Kashida H, et al. Nonpolypoid neoplastic lesions of the colorectal mucosa. Gastrointest Endosc. 2008 Oct;68(4 SUPPL.).
2. Ferlitsch M, Moss A, Hassan C, Bhandari P, Dumonceau JM, Paspatis G, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Vol. 49, Endoscopy. Georg Thieme Verlag; 2017. p. 270–97.
3. Lopez A, Bouvier AM, Jooste V, Cottet V, Romain G, Faivre J, et al. Outcomes following polypectomy for malignant colorectal polyps are similar to those following surgery in the general population. Gut. 2019 Jan 1;68(1):111–7.
4. Choi YS, Kim WS, Hwang SW, Park SH, Yang DH, Ye BD, et al. Clinical outcomes of submucosal colorectal cancer diagnosed after endoscopic resection: A focus on the need for surgery. Intest Res. 2020 Jan 1;18(1):96–106.
5. Gibson DJ, Sidhu M, Zanati S, Tate DJ, Mangira D, Moss A, et al. Oncological outcomes after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps with covert submucosal invasive cancer. Gut. 2022 Mar 7;

Disclosure

Conflicts of interest: None. Financial disclosures: None.

Introduction

Hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of activated immature myeloid cells that are characterized by different specific surface molecules, they express each of CD11b+CD33+ and lack expression of HLA-DR. MDSC are immunosuppressive cells that decrease immune cell activation and induce immunological tolerance in inflammation and cancer. Under normal conditions, MDSC remain in the bone marrow until differentiation; however, under pathological conditions these cells arrest at various stages of development, migrate out of the bone marrow in an immature state and, accumulate in circulation and peripheral lymphoid organs, causing negative regulation of immune responses via various mechanisms, primarily T cell suppression. MDSC are known to increase in patients with chronic hepatitis C virus infection. But it is not clear till now if eradication of HCV using directly acting antivirals can restore normal levels of MDSC on long term or not.

Aims & Methods

This study aimed to assess the levels of MDSC in patients with previous chronic hepatitis C after achieving sustained virologic response (SVR) for at least 2 years using sofosbuvir containing regimens.
This study was a case-control one. Fifty five subjects were involved in the study. All patients had completed DAAs therapy 2-3 years before involvement. Estimation of (CD33+ HLA-DR– CD11b+) expressing cells by flow cytometry was done and levels were compared between HCV patients achieved SVR for 2-3 years and healthy control without any current or previous chronic disease.

Results

MDSC were significantly higher among patients with eradicated HCV for 2-3 years than in healthy controls (4.98% (IQR=3.3 – 7.7) vs 3.09% (1.4 – 3.9), p = 0.001)

Conclusion

Normal MDSC levels are not restored after eradication of HCV using directly acting antivirals even after passage of 2 years on viral eradication. Clinical implications and consequences of these findings should be further investigated.

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

Surgical criteria for pancreatic cyst lesions are determined by the nodule in the cyst and dilation of the main pancreatic duct, but other imaging factors are needed to improve accuracy.

Aims & Methods

Aims: The present study aimed to identify factors of malignancy resection in intraductal papillary mucinous neoplasms (IPMN) treated at our center by evaluating the malignant portions of resected specimens pathologically to extract new imaging features that may serve as novel indices of malignancy.
Methods: Forty-eight patients with IPMN (14 pancreatic head, 31 body to tail, three total pancreatectomies) with a median age of 71 years (range: 38-84) and a male: female ratio of 35: 13 were enrolled. IPMN was divisible into the main pancreatic duct (n=11), branched duct (n=23), and mixed (n=14) types. Furthermore, 27, ten, and 11 cases of IPMA, high-grade IPMN (HG), and IPMC invasive group (C), respectively, were analyzed. [1] Clinical images of the benign group (A) were compared with those of the malignant group (HG+C) ［2]the malignant specimens and areas of invasion were pathologically analyzed (HG+C). ［3] The malignancy detection rate on DW-MRI was then examined; a higher intensity in the lesion than in the surrounding pancreatic parenchyma indicated positivity.

Results

[1] Age (median: 69 years vs. 73 years; P=0.06), history of pancreatitis (15% vs. 10%; P=0.68), and the preoperative serum mean AMY, CA19-9, and CEA positivity rates did not differ significantly between the benign and malignant groups. HbA1c (mean,%) was higher in the malignant group at 5.9 vs. 6.7 (P=0.03). In terms of imaging features, the proportion of main pancreatic ducts with a diameter >10 mm was 22% and 48% in the respective group (P=0.06); the mean cyst diameter was 33 mm vs. 28 mm (P=0.19); the proportion of contrast-enhanced nodules > 5 mm was 7.4% vs. 52.4% (P<0.01); the positivity rate on DW-MRI was 12% vs. 68% (P<0.01), the detection rate of pancreatic duct stenosis rate on MRI was 11% vs. 38% (P＜0.05); worrisome features (WSF) were found in 42% (20/48) of cases; and high-risk stigmata (HRS) were found in 52% (25/48) of cases. The malignancy rate in the WSF and HRS cases was 20% (4/20) and 68% (17/25), respectively.
[ 2] The histological subtypes of the malignant group were gastric (n=5), intestinal (n=8), oncocytic (n=6), and biliary pancreatic (n=2). Areas of high-grade dysplasia and invasion in the HG group and C group, respectively, were consistent with the presence of a nodule and area of pancreatic duct stenosis.
[ 3] When instances of malignancy were treated as positive, the sensitivity, specificity, positive predictive value, negative predictive value, and positive diagnostic value of HRS was 81%, 70%, 68%, 83%, and 75%, respectively, in the 44 cases while the diagnostic performance of DW-MRI was 68%, 88%, 81%, 79%, and 80% for the respective items. The positivity rate for groups A, HG, and C was 12%, 60%, and 78%, respectively.

Conclusion

The present study of resected IPMN found that DW-MRI provided surgical criteria with a diagnostic performance comparable to the HRS criteria.

Introduction

Microscopic colitis (MC) represents a spectrum of chronic inflammatory bowel diseases (IBD) characterized by chronic watery diarrhea and distinctive histologic features. The data concerning the epidemiology of microscopic colitis in Poland are non-existing or scarce.

Aims & Methods

The Polish Registry of Microscopic Colitis was established to better understand the clinical characteristics, treatment patterns, and outcomes of MC patients in Poland.
We present retrospective and prospective data findings from the initial cohort of 165 patients enrolled in the registry, spanning nine academic gastroenterology centers across Poland. Data collection included demographics, clinical presentation, histopathological features, treatment modalities, and clinical outcomes.

Results

The median age at diagnosis was 57 years, with 36% of patients diagnosed before age 45. The majority (80%) had a prior MC diagnosis, with an average delay of approximately 3 years from symptom onset to diagnosis. MC occurred 3.5 times more frequently in women. Lymphocytic colitis (LC) was the most common subtype (66.7%), followed by collagenous colitis (CC) (24.1%) and incomplete colitis (IC) (9.3%). Women were more predisposed to CC. Normal colonoscopy results were observed in 71.5% of patients. Approximately 48% were active or former smokers, with smokers more likely to have CC. Predominant symptoms included watery diarrhea (86.1%), fecal urgency (66.1%), abdominal pain (58.8%), and bloating (62.4%). Weight loss during exacerbation of symptoms was reported in nearly one-fifth of patients. One-third of MC patients reported abdominal pain consistent with Rome IV criteria for irritable bowel syndrome (IBS) during medical interviews. Additionally, nearly half of the patients had a confirmed Covid-19 infection based on authorized testing. Budesonide MMX demonstrated the highest efficacy (92.4% reported improvement), with other treatment modalities showing varied effectiveness. Three patients with severe MC were successfully treated with adalimumab.

Conclusion

The Polish Registry of Microscopic Colitis provides comprehensive insights into the clinical features and treatment outcomes of MC in Poland. Budesonide MMX emerged as an effective treatment option, while biologic therapy showed promise in refractory cases. Our findings suggest a potential overlap of symptoms between MC and IBS, highlighting the importance of thorough clinical assessment. Our findings inform evidence-based practice and highlight the importance of multidisciplinary collaboration in MC management. The multicenter nature of the Polish MC Registry provides a comprehensive overview of real-world practices and outcomes, facilitating future research and the development of standardized management strategies for this understudied condition.

References

1. Miehlke S., Guagnozzi D., Zabana Y. et al.: European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations. United European Gastroenterol. J., 2021; 9: 13–37.
2. Larsson JK, Clarkson S, Sjoberg K: Regional differences in the incidence of lymphocytic and collagenous colitis over time. Scand J Gastroenterol. 2023; 58(12):1445-1452.
3. Weimers P, Vedel Ankersen D, Lophaven SN et al. Microscopic Colitis in Denmark: Regional Variations in Risk Factors and Frequency of Endoscopic Procedures. J Crohns Colitis. 2022; 16(1):49-5

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.

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