Introduction

Large lateral spreading tumours (LSTs) of the colon with focal suspicion of submucosal invasion present a clinical challenge. A hybrid endoscopic approach - combining endoscopic mucosal resection (EMR) for the benign-appearing areas and endoscopic full-thickness resection (eFTR) for the suspicious focus - may offer a viable alternative to oncologic surgery or endoscopic submucosal dissection, especially in cases where deep submucosal invasion is suspected. However, current evidence on the safety and efficacy of this hybrid approach remains limited.

Aims & Methods

Between November 2015 and July 2024, consecutive patients undergoing hybrid EMR-eFTR for colonic LSTs (>2cm) with suspected focal submucosal invasion or non-lifting lesions with histologically confirmed adenocarcinoma were retrospectively identified from the Dutch prospective eFTR registry and three German centres. Primary outcomes included technical success, R0 resection rate, and adverse events according to AGREE classification. Secondary outcomes included cancer recurrence, assessed via surveillance endoscopy, imaging and CEA levels in accordance with local protocols. Technical success was defined as macroscopic complete resection of the LST, R0 resection as histologically carcinoma-free resection margins (>0.1mm) of the eFTR specimen. Low-risk T1 cancer was defined as R0 resection in the absence of lymphovascular invasion, poor differentiation, or high-grade tumour budding (if assessed).

Results

A total of 59 patients were included (median age 72 years; 53% male), with a median lesion size of 25 mm (IQR 20). Most lesions were located in the proximal colon (40/59, 68%), while 19 (32%) were in the distal colon. Technical success was achieved in 51/59 (86%) cases. Adverse events occurred in 8 (14%) patients, including two (3%) perforations (one immediate, one delayed) requiring surgery (Grade IIIb) and one (2%) delayed bleeding event without an identifiable focus during endoscopy (Grade IIIa). Histopathological analysis identified adenomas in 9/59 (15%) patients and adenocarcinomas in 50/59 (85%), including 37/59 (63%) pT1 (sm1: 35% [13/37]; sm2-3: 65% [23/37]) and 13/59 (22%) ≥pT2 cancers. Among pT1 cancers, 19/37 (51%) were considered low-risk. The overall R0 resection rate was 43/59 (73%), with R0 resection achieved in 27/37 (73%) pT1 cancers (sm1: 92% [12/13]; sm2-3: 65% [15/23]) and 7/13 (54%) pT2 cancers. Vertical margin involvement accounted for 40% of incompletely resected pT1 cancers. Following hybrid EMR-eFTR, 22/59 (37%) patients underwent completion surgery, while 37 (63%) were managed with surveillance only. In the surveillance-only cohort (non-invasive: 8, low-risk T1: 16, high-risk T1: 10, T2: 3), no locoregional cancer recurrences were observed during a median follow-up of 24 months (IQR 43). One patient with high-risk T1 cancer developed liver metastases at 41 months.

Conclusion

Hybrid EMR-eFTR demonstrated promising technical feasibility and short-term oncological outcomes in the management of large colonic LSTs with focal submucosal invasion. This organ-preserving approach may be particularly valuable given the high prevalence of sm2-3 invasion among pT1 colon cancers. Improving visual delineation of the malignant component may further improve R0 resection rates. Prospective studies are warranted to evaluate long-term oncological safety.

Disclosure

I have nothing do declare

Introduction

Pancreatic exocrine insufficiency (PEI) is a condition characterized by inadequate secretion or activity of pancreatic enzymes, resulting in the maldigestion and malabsorption of nutrients. While PEI is most commonly associated with chronic pancreatitis and cystic fibrosis, it also occurs frequently in the context of pancreatic and peri-pancreatic malignancies. In patients with pancreatic cancer PEI arises due to direct tumor infiltration, ductal obstruction, parenchymal destruction, or as a consequence of surgical resection. Other gastrointestinal malignancies, such as ampullary or biliary tree cancers, may also contribute to PEI through similar mechanisms. Importantly, PEI in cancer patients is often under-recognized, despite its significant impact on nutritional status, quality of life, and overall prognosis. Timely identification and management of PEI in malignancy-associated cases is crucial to optimize clinical outcomes and support ongoing cancer therapies.

Aims & Methods

The objective of this study is to assess the incidence of PEI in patients with biliopancreatic and ampullary tumors, to explore potential differences in PEI occurrence based on tumor location and to investigate possible associations between PEI and relevant biomarkers.
We conducted a retrospective observational analysis of a consecutively recruited patient cohort including patients diagnosed with biliopancreatic and ampullary tumors at a tertiary care hospital between 2016 and 2024.
PEI was defined as fecal elastase-1 (FE-1) levels below 100 µg/g.
At the time of diagnosis, we collected data on demographic characteristics, tumor-related variables, the incidence of PEI, and serum nutritional markers.

Results

We included 408 patients with malignancies potentially associated with PEI. Of these, 54.2% were male, with a mean age of 72 years (range: 38–101) and a mean body mass index (BMI) of 25.45 (SD ± 4.28).
The types of malignancies included were pancreatic ductal adenocarcinoma (PDAC) in 63.5% of patients, cholangiocarcinoma (CCA) in 23.8%, ampullary tumors in 9.8%, and gallbladder tumors in 2.9%. The overall incidence of PEI at the time of diagnosis was 38.2%. Among subgroups, the incidence was 51.4% in PDAC patients, 13.4% in those with CCA, and 25% in those with ampullary tumors. PEI incidence was significantly associated with elevated HbA1c (>5.8%, p<0.01) and Ca 19-9 levels (>37 U/mL, p<0.01).
In PDAC, tumors located in the pancreatic head were associated with a significantly higher incidence of PEI (58.8%) compared to tumors in the body (27.8%) and tail (21.7%) (p<0.01). In this subgroup, PEI was significantly associated with elevated HbA1c (>5.8%, p=0.03), elevated Ca 19-9 (>37 U/mL, p=0.04), and elevated bilirubin (>1.2 mg/dL, p<0.01).
In contrast, among CCA patients, no significant differences in PEI incidence were observed based on tumor location, and no significant associations were found between PEI and the clinical or laboratory variables analyzed .

Conclusion

• PEI is observed not only in patients with PDAC but also in those with CCA and ampullary tumors at the time of diagnosis.
• Given the high incidence of PEI in tumors located in the pancreatic head, empirical pancreatic enzyme replacement therapy should be considered in this subgroup.
• In PDAC patients, the presence of PEI is significantly associated with endocrine dysfunction, hyperbilirubinemia secondary to biliary obstruction and elevated Ca 19-9 levels.

Introduction

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide^1,2. Liquid–liquid phase separation (LLPS) describes a reversible and dynamic process in which intracellular biomacromolecules condense into liquid-like biomolecular assemblies through multivalent interactions³. Emerging evidence indicates that dysregulated phase separation may play a pivotal role in cancer initiation and progression^4-6. However, the specific role and regulatory mechanisms of LLPS in the progression and metastasis of CRC remain largely unexplored.

Aims & Methods

Magnifying endoscopy combined with narrow-band imaging (ME-NBI) was used to perform targeted biopsies of distinct colorectal tissue subpopulations. Adjacent normal tissues, non-invasive cancer, and invasive colorectal cancer samples were separately collected for ATAC-seq and RNA-seq to identify core transcription factor (TF) involved in the progression of CRC. Then, the TF was purified in vitro and over-expressed in vivo separately to observe the phase separation phenomenon. Besides, phase separation-deficient mutants were identified and characterized to determine their biophysical properties. Finally, we evaluated its effects on CRC invasion and metastasis both in vitro and in vivo by using transwell migration and invasion assays, wound healing assays, and a lung metastasis model in nude mice.

Results

Multi-omics analysis identified ETV4 as a key driver of CRC progression. qRT-PCR and Western blot revealed that ETV4 were significantly elevated in CRC tissues compared to adjacent normal tissues. Correlation analysis based on data from The Cancer Genome Atlas (TCGA) further demonstrated that high ETV4 expression was positively associated with distant metastasis and advanced tumor stage in CRC. Meanwhile, the purified ETV4 readily formed droplet-like condensates in vitro. Transfection of HEK-293T and CRC cell lines with ETV4-GFP plasmids similarly resulted in the formation of distinct intracellular droplet-like condensates. Besides, fluorescence recovery after photobleaching (FRAP) assays using confocal laser microscopy demonstrated that fluorescence signals in the bleached regions of ETV4 condensates gradually recovered over time, indicating that these condensates exhibit dynamic liquid-like properties.
Based on the intrinsically disordered regions (IDRs) of ETV4, a series of truncated mutants (ΔIDR1, ΔIDR2, and ΔIDR3) were constructed. When these mutant plasmids were transfected into HEK-293 cells, only deletion of the IDR1 region (ΔIDR1) abrogated the formation of droplet-like condensates. Notably, expression of the IDR1 region alone was sufficient to restore condensate formation within cells, indicating that IDR1 is essential and sufficient for ETV4-mediated phase separation. Furthermore, in vitro experiments demonstrated that ETV4 overexpression significantly enhanced the migratory and invasive capacities of colon cancer cells, whereas ETV4 knockdown markedly suppressed these malignant phenotypes compared to control groups. Additionally, mice injected with ETV4 wild-type (ETV4-FL) cells developed significantly more lung metastases compared to controls, whereas those injected with the phase separation-deficient mutant (ETV4-ΔIDR1) failed to enhance metastatic dissemination.

Conclusion

This study identifies ETV4 as a pivotal transcriptional regulator that drives CRC progression and metastasis. Besides, ETV4 undergoes LLPS both in vitro and in vivo, with this process being specifically mediated by its first IDR1. Importantly, the pro-metastatic function of ETV4 is mechanistically dependent on its LLPS capability.

References

• 1. Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74, 229–263 (2024).
• 2. Biller, L. H. & Schrag, D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA 325, 669–685 (2021).
• 3. Mehta, S. & Zhang, J. Liquid-liquid phase separation drives cellular function and dysfunction in cancer. Nat Rev Cancer 22, 239–252 (2022).
• 4. Zong, Z. et al. Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis. Cell 187, 2375-2392.e33 (2024).
• 5. Liu, Q. et al. Glycogen accumulation and phase separation drives liver tumor initiation. Cell 184, 5559-5576.e19 (2021).
• 6. Ahn, J. H. et al. Phase separation drives aberrant chromatin looping and cancer development. Nature 595, 591–595 (2021).

Clinical Case Summary

Case presentation: An 18-year-old male with a four-year history of recurrent nausea, vomiting, and upper abdominal pain, worsened after meals, was diagnosed with Superior Mesenteric Artery Compression Syndrome (SMAS).
Diagnosis and treatment: The diagnosis of SMAS was confirmed by CT and CTA, which revealed a reduced aortomesenteric angle and duodenal compression, excluding other gastrointestinal conditions like peptic ulcers and pancreatitis. An upper GI contrast study showed delayed gastric transit, and endoscopy revealed mild mucosal edema without obstruction. Blood tests showed elevated WBC (14.99 × 10⁹/L) and low albumin (61.5 g/L), indicating inflammation and malnutrition.
Given the failure of conservative treatment, the patient underwent laparoscopic duodenojejunostomy on March 14, 2025. The surgery was successful with minimal blood loss. Postoperatively, the patient received somatostatin, antibiotics, and nutritional support, with gradual transition from parenteral to enteral feeding. Follow-up imaging confirmed a successful anastomosis, and the patient experienced significant symptom relief and improved nutritional status.
Outcome and discussion: The patient was discharged after 38 days with substantial improvement in symptoms and quality of life. This case highlights the importance of considering SMAS in young patients with persistent postprandial symptoms. Early surgical intervention, such as duodenojejunostomy, is effective for relieving duodenal compression and improving outcomes, particularly when conservative treatment fails.The poster will include the patient's abdominal enhanced CT scan, 3D reconstruction images, pathological images, and postoperative drainage volume changes.

Introduction

Diagnosing the extent of early gastric cancer (EGC) using narrow-band imaging with magnification (NBI-M) can be challenging in cases with large lesions or severe surrounding gastritis. Moreover, if the endoscope tip contacts the lesion and causes bleeding, the quality of the diagnosis of EGC by NBI-M is degraded. The NBI-M method requires the endoscopist's skill because of the delicate manipulation of the endoscopic scope. In contrast, the acetic acid with indigocarmine (AIM) method is a simpler technique that facilitates extent diagnosis regardless of expertise. However, AIM does not yield effective results in all EGC cases.

Aims & Methods

The study aimed to determine the optimal method for delineating EGC extent during endoscopic submucosal dissection (ESD) marking. Informed consent was obtained from 107 patients scheduled for gastric ESD at our institution. The extent of EGC was assessed first with NBI-M, followed by thorough rinsing and spraying with 2% AIM. One minute after spraying AIM, visibility of the lesion extent was graded on a four-point scale: 0= not identifiable, 1= unclear, 2= approximately clear, 3= clear. Resected specimens were immunohistochemically stained for MUC5AC, MUC6, MUC2, and CD10. The immunohistochemical score for each staining was determined as follows: 0= no staining, 1= ≤1/3, 2= 1/3–2/3, 3= ≥2/3 of cancer stained. We examined the relationship between the extent of each staining and the clarity of extent diagnosis of EGC using the AIM method. In addition, a logistic analysis was performed on the factors involved in the cases in which AIM method was superior to NBI-M for extent diagnosis of EGCs.

Results

Of the initial 107 patients, 102 with 102 lesions were analyzed after excluding two cases of signet ring cell carcinomas, one case of gastric carcinoma with fundic gland type, and two cases with consent withdrawal. There were no significant differences in the degree of staining with AIM for gender, infection of Helicobacter pylori, degree of atrophy, lesion size or histological type. Regarding lesion location, EGCs located in the upper third of the stomach showed significantly clearer staining with the AIM method (p=0.0018): 10 lesions (76.9%) were clearly stained, 2 lesions (15.3%) were approximately clear, and 1 lesion (7.6%) was not identifiable. As for the relationship between AIM staining and mucin phenotype expression, only CD10 expression was significantly more frequent in EGCs that showed clear staining with AIM (p=0.019). In the diagnosis of the extent of gastric cancer, AIM was superior in 37 cases, NBI-M was superior in 41 cases, and equivalent in 24 cases. The factors involved in cases with superior AIM method were CD10 (p=0.097, OR 1.14) and upper third of stomach (p=0.042, OR 9.33) in univariate analysis and only upper third of stomach (p=0.027, OR 12.18) in multivariate analysis.

Conclusion

The proposed strategy for determining the extent of EGCs is to prioritize the AIM method for lesions with high CD10 expression and located in the upper third of the stomach.

Introduction

The LiverRisk score was recently developed as a tool for predicting liver fibrosis and liver-related outcomes in the general population. We aimed to evaluate the predictive performance of the LiverRisk score for liver fibrosis and overall mortality in HCV patients treated with direct acting antivirals.

Aims & Methods

This was retrospective, descriptive and analytical study conducted in a gastroenterology department over 8 years including patients diagnosed with chronic hepatitis C. Data were collected from patient records and during their follow-up. The data normality test for this study was conducted using the Shapiro-Wilk test. The discrimination ability of the Liver Risk Score was evaluated using the Area Under the Receiver Operating Characteristic (AUROC) curve. Overall mortality was assessed at the conclusion of the follow-up period.

Results

Among 165 patients monitored for hepatitis C and treated with direct-acting antivirals, only 68(41.2%) patients were eligible for this study. Mean age at diagnosis was 61±13.2 year; sex ratio M/W was 0.78 .10(14.7%) of the patients were tobacco users. 22(32.4%) had hypertension, and 14(20.5%) had diabetes.
Regarding hepatic risk factors; 5(7.5%) had alcohol use disorder, and use of cannabinoid substances was reported in 5(3%) of the cases.1(1.4%) had history of drug injection. 7(10.6%) had a history of bloodletting and tattoos, and 4(6%) had high-risk sexual practices.
Regarding the circumstances of diagnosis, 23(39.7%) patients were diagnosed incidentally, 18(26.4%) following an evaluation for asthenia, 4(6.9%) presented with abdominal pain, and 3(4.4%) exhibited signs of portal hypertension.
In terms of laboratory findings, 25(36.7%) had cytolysis, 7(10.2%) showed biochemical cholestasis, 16(23.52%) had thrombocytopenia, and 5(7.3%) presented with sign of hepatocellular insufficiency. Hepatitis B coinfection was identified in 3(4.4%) cases.
The most frequent genotype was 1b, identified in 18(45%) patients, followed by genotype 2 in 17(25%). Genotypes 1a, 3, and 4 were observed in 5(7.3%) patients.
On ultrasound, 15(22%) patients showed signs of chronic liver disease, and 8(11.7%) exhibited signs of portal hypertension. A total of 26(38.2%) patients underwent upper endoscopy, among whom 13(19.11%) had esophageal varices, 2(2.9%) had gastric or gastroesophageal varices (GOV), and 9(13.2%) presented with hypertensive gastropathy.
46(75.4%) were treated with Sofosbuvir and Daclatasvir, followed by Sofosvubir and Velpatasvir for 9(14.8%). Sustained virological response was achieved for 51(91.1%) patients.
For fibrosis, 19(30.2%%) were at stage F4, 9(14.3%) at stage F3, 13(20.6%) at stage F2, and 22(34.9%) at stage F0-F1. Median Liver risk score was 7.58[6.28;8.5].
The LiverRisk Score exhibited high accuracy in predicting liver stiffness and outperformed traditional serum biomarkers of fibrosis. Its discriminatory capacity for detecting liver stiffness ≥10 kPa was reflected by an AUROC of 0.848, compared to 0.779 for the FIB-4 test. After 5 years follow up 8(11.76%) patients died. LiverRisk score was associated with the risk of all cause of mortality (HR= 1.34, 95% IC[0.98;1.83], p = 0.047).

Conclusion

The LiverRisk score is an accurate tool to predict liver fibrosis and mortality in HCV patients treated with direct acting antivirals.

Introduction

While the clinical trial (JCOG1009/1010) evaluating the efficacy and safety of endoscopic submucosal dissection (ESD) for intramucosal (T1a(M)) undifferentiated early gastric cancer (UD-EGC) of the predominant type measuring <2 cm not associated with ulceration showed a favorable 5-year survival outcome (99.3% (95% confidence interval: 97.1-99.8 )), the 10-year prognosis is still uncertain. We have followed the patients for 10 years.

Aims & Methods

Main eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤2 cm, no ulceration, and histological components of undifferentiated adenocarcinoma in biopsy. Based on the histologic findings after ESD, additional gastrectomy was indicated if the histopathologic examination did not meet the criteria for curative resection. The primary endpoint was 5-year overall survival (OS) of the undifferentiated-predominant type group, and 10-years follow-up of patients was planned.

Results

Of a total of 346 patients enrolled between February 2011 and May 2013 from 49 institutions, 337 were eligible and all eligible patients underwent ESD. Histopathologic findings of the resected specimens showed undifferentiated predominant cancer in 275 patients while one patient could not be evaluated due to emergent surgery for a perforation during ESD. Of the 275 patients, 195 whose ESD was judged to result in a curative resection were followed up without additional treatment, and 73 of the remaining 79 patients whose ESD was judged to result in a non-curative resection received additional gastrectomy. Among the 275 patients with UD-EGC, one patient experienced a metastatic recurrence 3,034 days after ESD. The 10-year OS and relapse-free survival (RFS) of patients with undifferentiated-predominant type were 96.2% (95% confidence interval: 93.1-97.9) and 95.7% (95% confidence interval: 92.4-97.6), respectively, while the 10-year OS and RFS for all 346 enrolled patients were 95.1 % and 94.7 %, respectively.

Conclusion

ESD for UD-EGC with tumor size of 2 cm or less is the standard treatment, with excellent 10-year survival results as well as in the 5-year period.