Introduction

Multiple pathways have been proposed to explain the development of colorectal cancer. The first is the well-established adenoma–carcinoma sequence, in which polypoid adenomas gradually progress to early polypoid cancers and eventually to advanced carcinomas. The second is the serrated pathway, where serrated lesions evolve into early cancers. The third is the de novo pathway, which hypothesizes that carcinomas arise directly from normal epithelium without a pre-existing adenomatous stage. This study focuses on the depressed-type colorectal cancers, which are thought to develop through the de novo pathway, and aims to elucidate their distinct clinicopathological features.

Aims & Methods

From April 2001 to December 2023, a total of 50,119 colorectal neoplasms (excluding advanced cancers) were resected either endoscopically or surgically at Showa University Northern Yokohama Hospital. Among them, 1,633 lesions were identified as T1 carcinomas. Based on macroscopic growth patterns, these T1 cancers were classified into three categories: depressed-type (n = 323; 20.1%), flat-type (n = 602; 36.9%), and protruded-type (n = 703; 43.0%). We compared the pathological characteristics and recurrence rates among the three groups.

Results

The mean tumor size was 15 mm in depressed-type lesions, 32 mm in flat-type, and 18 mm in protruded-type. Vascular invasion was significantly more frequent in the depressed-type group (42%) compared to both flat- and protruded-type lesions (21% each). The proportion of poorly differentiated or mucinous adenocarcinoma was also higher in the depressed type (14%) compared to flat (10%) and protruded types (15%). In contrast, the prevalence of adenomatous components was markedly lower in the depressed type (4%) than in the flat (54%) and protruded types (52%). Similarly, the frequency of polypoid morphology was only 13% in depressed lesions, compared to 56% and 88% in flat and protruded types, respectively. These findings suggest that depressed-type lesions may arise directly from normal epithelium, bypassing the adenomatous phase. The overall rate of distant metastasis or recurrence among all T1 cancers was low, at 0.8% (13 out of 1,633 cases).

Conclusion

Depressed-type colorectal carcinomas are characterized by significantly smaller tumor size and a lower prevalence of adenomatous components, yet exhibit a higher rate of vascular invasion and unfavorable histological features compared to flat and protruded types. These clinicopathological features support the hypothesis that depressed-type carcinomas follow a de novo pathway of tumorigenesis. Given their subtle appearance and high malignant potential, these lesions may be overlooked during routine colonoscopy. Therefore, careful attention should be paid to their morphological features during endoscopic examination to ensure early detection and appropriate management.

Clinical Case Summary

Introduction: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder with multisystem involvement, predominantly affecting the cardiovascular system. Aortic aneurysms and dissections are common complications. LDS shares features with other connective tissue disorders, such as Marfan and Ehlers-Danlos syndromes (1).
Case report: A 44-year-old male with a marfanoid habitus, history of thyroid carcinoma treated with radioactive iodine, appendectomy complicated by hematoma and dehiscence, and Loeys-Dietz syndrome type 3 (SMAD3 variant), diagnosed after a Stanford type A aortic dissection in 2022. In 2023, he underwent left carotid-subclavian bypass and ascending aortic aneurysm repair with hybrid graft. Family history included aortic dissection and hiatal hernia. He was on levothyroxine, dicoumarol, and omeprazole. Referred to the motility unit for preoperative evaluation of a large hiatal hernia seen on CT (Figure 1A).
He reported diet-related occasional nocturnal heartburn and regurgitation, well-controlled with PPIs. No dysphagia or alarm symptoms. Gastroscopy showed an 8–10 cm partially volvulated hernia sac without mechanical or vascular compromise. Esophagogram (1B) confirmed a mixed hiatal hernia with severe reflux and delayed esophageal clearance. High-resolution manometry with impedance (HRIM) showed a short esophagus (21 cm), ineffective motility, incomplete bolus transit and early post-swallow reflux (1C). Due to high risk of postoperative dysphagia, partial fundoplication was advised, but conservative management was chosen given prior surgical dehiscence and good symptom control.
Discussion: Gastrointestinal manifestations of LDS are rare and understudied. Large hiatal and abdominal wall hernias are among the most frequent findings, due to altered structural support at the esophagogastric junction (4,5). GERD symptoms are common and may require multidisciplinary care. HRIM is essential for preoperative planning in these patients.

References

1. Gouda, P., Kay, R., Habib, M., Aziz, A., Aziza, E., & Welsh, R. (2022). Clinical features and complications of Loeys-Dietz syndrome: A systematic review. International journal of cardiology, 362, 158–167. https://doi.org/10.1016/j.ijcard.2022.05.065
2. Wang, X. J., Babameto, M., Babovic-Vuksanovic, D., Bowen, J. M., & Camilleri, M. (2021). Audit of Gastrointestinal Manifestations in Patients with Loeys-Dietz Syndrome and Vascular Ehlers-Danlos Syndrome. Digestive diseases and sciences, 66(4), 1142–1152. https://doi.org/10.1007/s10620-020-06265-8
3. Honrubia Lopez, R., Burgos García, A., & Palacios Lázaro, E. (2017). Multiple perforation of small-intestine diverticula in a patient with Ehlers-Danlos syndrome. Revista espanola de enfermedades digestivas, 109(1), 83. https://doi.org/10.17235/reed.2016.4452/2016
4. Castori, M., Morlino, S., Pascolini, G., Blundo, C., & Grammatico, P. (2015). Gastrointestinal and nutritional issues in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. American journal of medical genetics. Part C, Seminars in medical genetics, 169C(1), 54–75. https://doi.org/10.1002/ajmg.c.31431
5. Thwaites, P. A., Gibson, P. R., & Burgell, R. E. (2022). Hypermobile Ehlers-Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know. Journal of gastroenterology and hepatology, 37(9), 1693–1709. https://doi.org/10.1111/jgh.15927

Clinical Case Summary

An 82-year-old man with Child B alcoholic cirrhosis, complicated by portal hypertension, underwent surveillance upper digestive endoscopy (UDE), revealing large esophageal varices and a 20 mm exophytic lesion, 40 cm from the dental arch, with an infiltrative and ulcerated appearance. Biopsies were inconclusive. Endoscopic ultrasound identified a heterogeneous, amorphous lesion with poorly defined borders and disruption of all wall layers, complicated by numerous large varices, preventing biopsy due to hemorrhagic risk. Computed tomography revealed parietal thickening in the distal esophagus and multiple varices, complicating lesion delineation. An oncology consultation recommended clinical surveillance, considering the patient's age, comorbidities, indeterminate nature of the esophageal lesion, and low suspicion for adenocarcinoma on ultrasound. One year later, surveillance UDE showed regression of the lesion.Histological samples were reviewed, revealing changes consistent with pyogenic granuloma. Pyogenic granuloma is a rapidly growing capillary hemangioma that may occur within the lumen of a pre-existing vessel (intravascular variant). The case is supported by appropriate iconography.

This case is presented with imaging, highlighting the challenge due to the macroscopic appearance suggestive of a neoplastic lesion and the pyogenic granuloma's growth within esophageal varices, limiting diagnostic and therapeutic management.

References

Introduction

Inflammatory Bowel Disease (IBD) patients carry a high risk of malnutrition, independently of disease activity. Screening for malnutrition in IBD is currently recommended since malnutrition, as well as low Fat-Free Mass Index (FFMI), have been associated to poor disease outcomes. However, due to a non-universal definition of malnutrition, most Nutritional Screening Tools (NSTs) have been validated compared to different reference methods and do not consider patients’ body composition. Moreover, the ability of most NSTs to predict malnutrition over time has not been explored.

Aims & Methods

The aim of this study was to compare the efficacy of different NSTs to predict malnutrition, as defined by the ESPEN 2015 and GLIM criteria, and a low FFMI in a cohort of inactive/mildly active IBD patients.
This is a prospective, single center, cohort study enrolling Crohn’s disease (CD) and ulcerative colitis (UC) patients in clinical remission or with mildly active disease as defined by Harvey-Bradshaw Index and partial Mayo Score, respectively. MUST, MIRT, MNA, NRS-2002 and SaskIBD-NR questionnaires and Bioelectrical Impedance Analysis (BIA) were performed at baseline and after six months follow-up. A low FFMI was defined as <18 kg/m2 in males and <15 kg/m2 in females. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the accuracy of the different NSTs for the detection of malnutrition and low FFMI at six months were calculated.

Results

Sixty-six (CD: 32; UC: 34) IBD patients were enrolled. Median age was 55.5 years (IQR 34-62.8), median disease duration was 10 years (IQR 6-17). At baseline, all CD and 30/34 (88%) UC patients were in clinical remission; median C-reactive protein was 0.8 mg/L (IQR 0-3.8), median fecal calprotectin was 55.2 mcg/g (IQR 12.9-326). Of the entire cohort, 6/66 (9%) and 17/66 (26%) patients were malnourished according to GLIM and ESPEN criteria, respectively, [(GLIM CD:3, UC: 3)(ESPEN: CD: 3; UC:14)] and 5/66 (8%) had low FFMI (CD:1; UC: 4). At 6 months follow-up, all CD and 31/34 (91%) UC patients were in clinical remission. Ten out of 66 (15%) and 32/66 (48%) patients were malnourished according to GLIM and ESPEN criteria, respectively [(GLIM CD:5, UC: 5)(ESPEN: CD: 15; UC:17)], 11/66 (17%) patients had low FFMI (CD: 3; UC: 8). Baseline MIRT showed the highest sensitivity for the diagnosis of both ESPEN and GLIM-defined malnutrition at 6 months (ESPEN: 40.5%; GLIM: 50%). For ESPEN, MIRT and NRS2002 were the most accurate NSTs (MIRT: 50%, NRS2002: 51.5%), while SaskIBD (75.8%) showed the highest accuracy in detecting GLIM-malnourished patients at 6 months follow up. Among all NSTs, baseline MIRT, MNA and NRS2002 had the highest sensitivity for the detection of low FFMI at six months (MIRT, MNA, NRS2002: 45.5%), while SaskIBD_NR was the most accurate (80.3%).

Conclusion

MIRT might be the NSTs of choice to predict defined malnutrition and low Fat-Free Mass Index at 6 months follow-up in a cohort of inactive/mildly active IBD patients.

References

Huang S, Niu Y, Liu X, Gu Z, Huang A, Wu J. Characteristics of malnutrition according to Global Leadership Initiative on Malnutrition criteria in non-surgical patients with inflammatory bowel disease. Nutrition. 2022;94:111514. doi:10.1016/j.nut.2021.111514

Jensen GL, Cederholm T, Correia MITD, et al. GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community. JPEN J Parenter Enteral Nutr. 2019;43(1):32-40. doi:10.1002/jpen.1440

Cederholm T, Bosaeus I, Barazzoni R, et al. Diagnostic criteria for malnutrition - An ESPEN Consensus Statement. Clin Nutr. 2015;34(3):335-340. doi:10.1016/j.clnu.2015.03.001

van Bokhorst-de van der Schueren MA, Guaitoli PR, Jansma EP, de Vet HC. Nutrition screening tools: does one size fit all? A systematic review of screening tools for the hospital setting. Clin Nutr. 2014;33(1):39-58. doi:10.1016/j.clnu.2013.04.008

Ding NS, Tassone D, Al Bakir I, et al. Systematic Review: The Impact and Importance of Body Composition in Inflammatory Bowel Disease. J Crohns Colitis. 2022;16(9):1475-1492. doi:10.1093/ecco-jcc/jjac041

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.