Introduction

Endoscopic submucosal dissection (ESD) has become a common treatment method for superficial esophageal cancer, allowing complete resection and accurate postoperative pathological evaluation, especially for relatively larger lesions^{1, 2}. However, resection of larger lesions, especially circumferential lesions, can be time-consuming and challenging. The resected tissue can obstruct the esophageal lumen, leading to limited working space and poor visibility, thereby increasing the risk of adverse events such as perforation and muscular injury³. In recent years, several auxiliary traction techniques have been emerged, including positional adjustment traction, hemostatic clip elastic band traction, snare traction, line traction, and magnet anchor traction, which significantly improve the visibility of the submucosal layer during dissection and enhance the efficiency of the procedure ^4-5. Among these techniques, snare traction allows bidirectional traction through "push and pull" maneuvers, offering flexibility and practicality in clinical practice. However, due to the difficulty and limited cases of circumferential esophageal ESD, there is currently no published literature demonstrating the advantages of snare traction-assisted ESD over traditional ESD techniques.

Aims & Methods

This study aims to investigate the efficacy and safety of snare traction assisted ESD for the management of circumferential superficial esophageal cancer. A total of 68 patients who underwent ESD for circumferential superficial esophageal cancer were included in this study. All the patients were divided into two groups based on whether the snare traction was used or not; the snare traction group (S-ESD, group n=35) and the control group (C-ESD, group n=33).

Results

There was no significant difference in the size of the resected area between the groups [21.98 (18.30, 27.00) cm² vs 24.00 (15.28, 30.72) cm², P=0.976]. The snare traction group had a shorter dissection time [92.00 (74.00, 121.00) min vs 110.00 (92.50, 137.00) min, P=0.017] and a faster resection speed [0.28±0.13 cm²/min vs 0.22±0.11cm²/min, P=0.040] compared to the control group. There were no statistically significant differences between the two groups in terms of hospital stay, cost, en bloc resection rate, R0 resection rate, curative resection rate，bleeding rate, perforation rate, stricture rate, and recurrence rate (P>0.05).

Conclusion

Snare traction-assisted ESD is a safe and efficient approach for the treatment of circumferential superficial esophageal cancer. Its advantages includes shorter procedure so the anesthesia requirement, clear operative filed view, improved mucosal dissection efficiency, simple, and easily accessible equipment.

References

1 Ishihara R, Arima M, Iizuka T et al. Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer. Dig Endosc. 2020; 32: 452-93.
2 Draganov PV, Wang AY, Othman MO, Fukami N. Aga institute clinical practice update: Endoscopic submucosal dissection in the united states. Clin Gastroenterol Hepatol. 2019; 17: 16-25.e1.
3 Zhang W, Zhai Y, Chai N et al. Endoscopic submucosal tunnel dissection and endoscopic submucosal dissection for large superficial esophageal squamous cell neoplasm: Efficacy and safety study to guide future practice. Surg Endosc. 2018; 32: 2814-21.
4 Fukami N. What we want for esd is a second hand! Traction method. Gastrointest Endosc. 2013; 78: 274-6.
5 Jin P, Yu Y, Fu KI, Yu DL, Li AQ, Sheng JQ. A new traction method with use of the snare as a "second hand" during endoscopic submucosal dissection. Endoscopy 2015; 47 Suppl 1 UCTN: E286-7.

Introduction

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Oxysterol binding protein 3 (OSBPL3) is a protein involved in lipid binding and transport and is known to play an essential role in tumorigenesis. However, its expression and function in colorectal cancer (CRC) is unclear.

Aims & Methods

This study included patients who underwent CRC surgery at Gachon University Gil Medical Center between April 2010 and January 2013. We analyzed 448 patients with primary colorectal cancer (CRC) who underwent surgery and had preserved paraffin blocks. Using immunohistochemical staining, a clinically applicable, rapid, and highly accurate assay method, we aimed to detect OSBPL3 expression in CRC and correlate it with clinicopathologic characteristics, prognosis, and survival to identify novel patient-specific biomarkers.

Results

The 5-year event-free survival (EFS) and disease-specific survival (DSS) hazard ratios (HRs) of the OSBPL3^High subgroup were 1.65 (95% confidence interval (CI): 0.99-2.76, p = 0.05) and 1.49 (95% CI: 0.89-2.61, p = 0.20), respectively. When tumor node metastasis (TNM) staging and OSBPL3 expression were combined, the 5-year EFS and DSS HRs of patients with CRC with OSBPL3^High expression cancer at the same TNM stage (stage III/IV) were 4.06 (95% CI: 2.72-6.07, p = 0.001) and 4.41 (95% CI: 2.91-6.68, p = 0.001), respectively, compared to those with OSBPL3^Low expression cancer, indicating a poor prognosis. Therefore, OSBPL3^High expression is associated with poor prognosis and survival rate in CRC patients. Combining OSBPL3 expression with TNM staging can predict CRC prognosis and survival rate more accurately.

Conclusion

Our data show that increased expression of OSBPL3 is associated with poor prognosis and survival rate in CRC patients. By combining OSBPL3 expression with TNM staging, we can more accurately predict the prognosis of CRC.

Introduction

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms, such as gastrointestinal symptoms. Emerging evidence suggests that gut permeability and inflammation play a role in PD pathophysiology via the gut-brain axis. According to Braak’s theory, the pathological degeneration associated with PD may originate from the gut and subsequently develop in the brain through the vagus nerve.

Aims & Methods

The aims were to assess the relationship between gut permeability and neuroinflammation in a cohort of patients with PD and REM behavior disorder (RBD), a condition that often precedes the onset of PD. The study prospectively included 28 PD patients and 18 RBD patients both complaining of GI symptoms. No serious organic diseases or therapies potentially affecting GI motility were reported. Relevant demographic and clinical data were collected for all patients. There was the inclusion of 14 healthy controls (HCs). A serum ELISA assay of tumor necrosis factor (TNF), caspase-1, and lipopolysaccharide-binding protein (LBP) was performed in all participants to investigate systemic inflammatory status and gut permeability, respectively. In a total of 10 PD patients, 4 RBD patients and 9 HCs, multiple colic biopsies were obtained to assay tissue expression of inflammation markers by both western blot (WB) (i.e. caspase-1 and procaspase-1) and immunofluorescence (IF) (i.e. ASC and CD68). Data were expressed as mean ± SD, and ANOVA and Dunnett's tests were used to compare the three groups.

Results

All three groups were comparable in age and sex. Serum assays showed significantly increased LBP, in patients with PD (35.0 ± 0.25; p = 0.002) and RBD (32.2 ± 1.1; p = 0.009) compared with HCs. TNF (0.1 ± 0.02; p = 0.03) and caspase-1 (16.9 ± 9.4; p = 0.04) were significantly raised only in the PD group in comparison with HCs (Table 1). WB analysis showed significant differences in the expression of procaspase-1 (157.3 ± 17.8; p = 0.02) and caspase-1 (168.3 ± 23.3; p = 0.03) only in PD patients compared with HCs. IF showed a qualitative increase in both CD68+ macrophage infiltration and ASC expression in PD and RBD groups compared with HCs.

	PD	RBD	HCs	P-value
LBP (ng/ml)	35.0 ± 0.25	32.2 ± 1.1	23.1 ± 2.1	0.009 (RBD vs HCs) 0.002 (PD vs HCs)
Caspasi-1 (ng/ml)	16.9 ± 9.4	11.4 ± 2.1	9.9 ± 2.7	0.04 (PD vs HCs)
TNF (pg/ml)	0.1 ± 0.02	0.05 ± 0.02	0.04 ± 0.02	0.03 (PD vs HCs)

Conclusion

Our results show a bowel activation of NLRP3 inflammasome in PD, as demonstrated both by the levels of procaspase-1 and caspase-1 on WB analysis and by the increase of CD68+ macrophages and ASC in the lamina propria of colonic mucosa. Only a qualitative increase in NLRP3 activation at IF could be observed in RBD patients. However, findings from colonic biopsies, if related to elevated serum levels of TNF and caspase-1 in PD patients, and LBP in PD and RBD patients, suggest that bowel inflammation, sustained by increased gut permeability, may represent an early stage in the develop of RBD and PD.

Introduction

The detection of cancer within large non-pedunculated colorectal polyps (LNPCPs) is suboptimal in non-expert settings. Identification of 6 macroscopic (Blink) features (6BF) of deep submucosal invasive cancer (SMI) has shown significant improvement in the sensitivity of cancer detection by inexperienced endoscopists at the expense of decreased specificity. This study investigates the impact of endoscopic resection scars, which can resemble deep SMI, on the accuracy of non-expert endoscopists using the 6BF evaluation system known as Blink Impression.

Aims & Methods

An online survey was disseminated containing 20 overview images of LNPCPs (1 image/polyp). Images (randomized) were shown before, and after a 2-minute educational video (the intervention) introducing the 6BF - fold deformation, extra redness, depression, chicken skin mucosa, ulceration and spontaneous bleeding. Before and after the intervention participant Blink Impression was elicited (cancer/no cancer) and only after, the presence of the 6BF. Responses were analysed relative to histopathology (no vs superficial vs deep SMI) and expert opinion on the presence of the 6BF and endoscopic resection scars.

Results

7/20 LNPCPs contained cancer (3 superficial, 4 deep SMI), 3 contained scars. 191 participants from 21 countries completed 3,755 observations. 129/191 (67.5%) participants were inexperienced. Expert-identified scarred LNPCPs contained median 1.0 (IQR 2.0) BF vs 1.0 (IQR 2.0) for no cancer, 2.0 (IQR 2.0) for superficial SMI and 3.0 (IQR 2.0) for deep SMI (all P<.001). Presence of ≥2 BF therefore reliably identifies cancer within LNPCPs but not scars. Fold deformation was the only BF identified more commonly amongst scarred LNPCPs (44.6%) vs no cancer (22.5%, P<.001) and vs superficial SMI (33.0%, P<.001), but similar to deep SMI (44.6%, P=1.000). Depression, chicken skin mucosa and spontaneous bleeding were less commonly identified in scarred polyps (12.3%, 7.6% and 1.8%) than both no cancer (33.1%, 14.4% and 8.6%, all P<.001), superficially invasive (68.6%, 14.3% and 5.8%, all P<.001) or deeply invasive polyps (45.9%, 19.6% and 40.5%, all P<.001). Extra redness and ulceration were identified with similar frequency to no cancer in scars (26.4% vs 26.8%, P=0.891 and 10.2% vs 9%, P=0.441 respectively), but less commonly than superficial (64.2%, P<.001 and 15.7%, P<.001) or deep SMI (60.2%, P<.001 and 24.7%, P<.001) (Table 1).

Conclusion

The presence of ≥2BF reliably discriminates LNPCPs with cancer from non-cancer even in the presence of scarred lesions amongst non-expert endoscopists. Scarred LNPCPs exhibit fold deformation at a similar rate to LNPCPs with deep SMI but other BF are not present.

References

Debels LK, Smeets S, Poortmans PJ, Argenziano ME, Desomer L, Anderson J, Valori R, David J Tate. Identification of 6 key features of colorectal polyps increases the sensitivity of cancer detection and ability to discriminate deep submucosal invasion The basis of the Blink (first) impression? United European Gastroenterology Journal 2023; Vol.11

Introduction

Ulcerative colitis, a type of inflammatory bowel disease, is characterised by chronic colonic inflammation often resulting in uncontrolled crypt lengthening and the development of colitis-associated colorectal cancer (CA-CRC). Orally administered Emu Oil, derived from Emu adipose tissue, has demonstrated protective and reparative properties in preclinical models of bowel disease, including CA-CRC. However, its long-term potential to reduce colonocyte proliferation and inhibit CA-CRC progression remains undetermined. Protein Ki-67 has been used widely as a proliferation marker for human tumour cells and may serve as a potential predictive biomarker for cancer progression.

Aims & Methods

We hypothesized that orally administered Emu Oil would reduce colonocyte proliferation, evidenced by decreased Ki-67 expression, in a mouse model of CA-CRC. Female C57BL/6 mice were injected with saline or azoxymethane (7.4mg/kg; intraperitoneal), followed by ad libitum access to either water or three dextran sulphate sodium (DSS)/water cycles (each cycle comprising seven days DSS [2%w/v] and 14 days water). Mice (n=9/group) were orally administered either water (80μL) or Emu Oil (low 80μL or high 160μL dose) thrice weekly for nine weeks. Proximal and distal colonic sections were stained with haematoxylin and eosin for crypt depth, cell count and size measurements and stained immunohistochemically to detect and quantify the proliferation marker Ki-67 in upper and lower colonocyte crypt zones. p<0.05 was considered statistically significant.

Results

In the proximal colon, numbers of Ki-67-positive cells in the upper and lower crypt regions of CA-CRC mice were increased by up to 100% compared with normal controls; low dose Emu Oil significantly decreased numbers of Ki-67-positive cells by 47% (p<0.05) compared with CA-CRC controls. Numbers of Ki-67-positive cells in the distal colon increased only in the upper crypt region in CA-CRC controls compared with normal mice (157%), with no further impact following Emu Oil administration (p>0.05). The overall percentage of Ki-67-positive cells remained unchanged in proximal and distal colonic crypts across treatment groups (p>0.05). Proximal and distal colonic crypt depth increased in mice with CA-CRC (20% and 37%, respectively; p<0.01), with greater distal colonocyte count, compared with normal controls (37%; p<0.05). Emu Oil did not impact proximal and distal colonic crypt depth nor cell counts in normal or CA-CRC mice (p>0.05). Furthermore, proximal colonocyte count, proximal and distal colonic cell diameter, and number of cells per 100μm remained unchanged among treatment groups (p>0.05).

Conclusion

Crypt lengthening in CA-CRC was primarily attributed to crypt cell hyperplasia, determined by increased cell numbers with no change in cell size. Low-dose Emu Oil administration in mice with CA-CRC resulted in attenuation of proximal colonic crypt cell proliferation, with no impact on crypt depth or cell size. Importantly, crypt depth and proliferation in normal mice remained unchanged following Emu Oil treatment, supporting its safety for long-term use to treat intestinal disorders. Future studies would benefit from an assessment of Emu Oil and its impact on expression of the oncogene Kras, tumour suppressor genes p53 and Apc, and inflammatory cytokines, including interleukin- 6, tumor necrosis factor-alpha and interferon-gamma, which are implicated in colorectal cancer progression.

Introduction

Peroxisome proliferator-activated receptor delta (PPARδ) agonists, such as seladelpar, emerged as potential therapies for PBC and other cholestatic diseases. PPARδs are nuclear receptors widely expressed in hepatocytes, cholangiocytes, Kupffer cells, and hepatic stellate cells. Activation of this receptor may modify the progression of PBC, particularly through its bile acid retention mechanism and antifibrotic and anti-inflammatory effects, inducing biochemical and clinical improvement in PBC patients.

Aims & Methods

We aimed to compare the efficacy and safety of seladelpar vs placebo for treating patients with primary biliary cholangitis (PBC) and inadequate response or intolerance to ursodeoxycholic acid (UDCA). We systematically searched MEDLINE, Embase, and Cochrane databases from inception to March 12, 2024. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were employed for dichotomous and continuous outcomes, respectively, using a random-effects model. We used Review Manager 5.4.1 for statistical analyses.

Results

We included 3 randomized clinical trials (395 patients). The results of the pooled analyses are shown in Table 1. Compared with placebo, seladelpar increased the probability of achieving composite biochemical response both at week 4 (RR 6.7; 95% CI 4.0 to 11.1) and at week 12 (RR 6.1; 95% CI 3.7 to 9.9), decreased alkaline phosphatase levels both at week 4 (MD -34.3%; 95% CI -39.6 to -29.0%) and at week 12 (MD -40.8%; 95% CI -47.9 to -33.6), increased the probability of achieving alkaline phosphatase normalization at week 12 (RR 18.6; 95% CI 3.8 to 90.4), and decreased pruritus scores at week 12 in both the overall population (MD -0.6; 95% CI -1.1 to -0.2) and the population with baseline pruritus score ≥4 (MD -1.2; 95% CI -2.0 to -0.4). Additionally, there was a non-significant difference between seladelpar and placebo in the risk of any adverse event (RR 1.0; 95% CI 0.9 to 1.1), any serious adverse event (RR 0.9; 95% CI 0.3 to 2.4), or any adverse event leading to treatment discontinuation (RR 0.7; 95% CI 0.2 to 2.0).

Table 1. Results from the pooled analyses

Conclusion

Seladelpar may be an effective and safe treatment option for patients with PBC and inadequate response or intolerance to UDCA. However, new large RCTs assessing long-term efficacy and safety outcomes are necessary to better evaluate its place in PBC management.

References

1. Hirschfield GM, Shiffman ML, Gulamhusein A, et al. Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study. Hepatology 2023;78:397–415.
2. Hirschfield GM, Bowlus CL, Mayo MJ, et al. A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis. N Engl J Med 2024;390:783–794.
3. Jones D, Boudes PF, Swain MG, et al. Seladelpar (MBX-8025), a selective PPAR-δ agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study. The Lancet Gastroenterology & Hepatology 2017;2:716–726.

Disclosure

The authors have no ​conflict of interest