Introduction

In recent years, the number of early-onset CRC (EO-CRC) diagnosed at the age of less than 50 years has been increasing. Previous studies suggest that EO-CRC may have higher malignant potentials and a worse prognosis than late-onset CRC. However, the reason why EO-CRC is regarded as aggressive cancer and result in delayed diagnosis remains unclear. We thought that both the lack of appropriate opportunities for screening or medical examination and the bias that was caused owing to being analyzed altogether regarding the different clinical stages could affect worse prognosis of EO-CRC. In this study, we focused on T1 cancer to highlight the essential features of EO-CRC to minimize the bias caused by the time of diagnosis.

Aims & Methods

This study is a secondary analysis of the main JSCCR (The Japanese Society for Cancer of the Colon and Rectum) project, “International joint research on lymph node metastasis in CRC”. Utilizing 4673 T1 CRC cases treated between July 2009 and December 2016 at 27 facilities belonging to JSCCR, we divided the patients into 5 groups according to age at the diagnosis: 49 years or younger, 50‒59 years, 60‒69 years, 70‒79 years, and 80 years or older. To analyze the clinicopathological features including sex, tumor location, macroscopic type, tumor size, histology, submucosal invasion depth, lymphatic/venous invasion, tumor budding, lymph node metastasis, and treatment methods, the Spearman’s correlation test was used. The difference of disease-free survival (DFS) between early-onset and later-onset CRC was also examined using log-rank test and Kaplan–Meier method.

Results

The cases of EO-CRC were 349 (7.5%). Among age groups, the proportion of rectum (from 49 years or younger to 80 years or older;44.1%, 42.0%, 36.6%, 29.0%, and 12.0%, respectively; P <0.05), protruded type (62.2%, 59.1%, 54.9%, 48.4%, 45.9%; P <0.05), and frequency of lymph node metastasis (10.0%, 7%, 8.0%, 7.0%, 4.6%; P <0.05) were decreased as the age group increased. In terms of sex, the proportion of male tends to decrease as the age group increased (57.9%, 60.8%, 63.5%, 57.0%, 52.7%, respectively; P <0.05). No significant differences were found among the five age groups for tumor size, histology, submucosal invasion depth, vascular invasion, tumor budding, recurrence rate, and treatment. No significant difference was observed regarding DFS between the two groups (5-year DFS; 98.7% for EO-CRC and 94.3% for late-onset CRC).

Conclusion

This study showed that the frequency of lymph node metastasis of T1 CRC decreased according to the increase of age at diagnosis, suggesting that EO-CRC may have a greater biological malignant potential compared to late-onset CRC. As far as we know, this is also the first study to report that “protruded type” would be one of the features of EO-CRC. Although no difference was observed as for DFS between two groups, it was plausible considering that only T1 stage CRC was enrolled in this study. Further studies are warranted to evaluate the clinicopathological features characterizing early stage EO-CRC.

Introduction

Short bowel syndrome (SBS) is a severe complication of extensive small intestinal resection, most commonly occurring in Crohn’s disease (CD), a chronic inflammatory disorder defined by transmural immune infiltration. Cytokines and chemokines are central mediators in the immune cascade driving intestinal inflammation and tissue damage^1,2. Despite advances in care, no biomarkers currently predict SBS onset or progression to intestinal failure (IF). Profiling systemic cytokine and chemokine signatures may thus offer novel insight into disease trajectory and risk stratification.

Aims & Methods

This study investigates circulating inflammatory mediators in patients with established IF/SBS and CD patients at high risk of progression. A total of 150 patients with CD were enrolled and stratified into five groups based on intestinal function and surgical history: A1, SBS with IF requiring parenteral nutrition (PN) or intravenous fluids; A3, SBS without IF and inactive disease; B, high risk of IF with multiple or extensive resections; C1, low risk for IF with no history of resection; and C2, low risk for IF with prior resection. Serum cytokine and chemokine profiles were quantified at baseline (T0) and after six months (T6) using the human 27-PLEX multiplex immunoassay.

Results

Serum cytokines and chemokines profiling at baseline (T0) and after six months (T6) revealed distinct inflammatory patterns across the study groups. Patients with SBS and IF (group A1) showed persistently elevated levels of IP-10, IL-12, MIP-1α, and G-CSF, reflecting sustained immune activation. Whereas, patients at high risk of IF (group B) displayed increased Eotaxin, bFGF, IL-15, and IL-6, indicative of subclinical inflammation and possible tissue remodelling.
A general reduction in cytokine levels was observed at T6, though anti-inflammatory mediators remained minimally modulated, suggesting ongoing low-grade inflammation. Comparisons between groups highlighted divergent cytokine signatures correlating with disease severity and nutritional support requirements.

Conclusion

These findings suggest that specific circulating cytokines may serve as potential biomarkers for early identification of patients at risk of IF. The differential expression patterns observed across groups support their relevance in stratifying disease severity in CD and SBS. Further large-scale studies are needed to validate these preliminary results and to fully establish their prognostic significance.
Funded by: 2.1 “Rafforzamento e potenziamento della ricerca biomedica del SSN”, finanziato dall’Unione europea – NextGenerationEU, CUP C53C22001140007. 2022 PNRR Project “Changing the future of intestinal failure in intestinal chronic inflammation: towards innovative predictive factors and therapeutic targets” code: PNRR-MAD-2022-12376791.

References

1. Friedrich M, Pohin M, Powrie F. Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. Immunity. 2019;50(4):992-1006. doi:10.1016/j.immuni.2019.03.017
2. Singh UP, Singh NP, Murphy EA, et al. Chemokine and cytokine levels in inflammatory bowel disease patients. Cytokine. 2016;77:44-49. doi:10.1016/j.cyto.2015.10.008

Introduction

The extent of gastric atrophy(GA) is closely related to the incidence of Intestinal-type gastric cancer (GC). According to the Kimura-Takemoto classification, determining whether the atrophy extends beyond the cardia is key to assess the extent of GA. However, there is significant difficulty in determining whether the cardia is atrophied under endoscopy.

Aims & Methods

This study developed a novel artificial intelligence (AI)-assisted white light endoscopy system for identifying the cardia part and diagnosing cardia atrophy . In this multicenter study, patients undergoing upper gastrointestinal endoscopy at 5 hospitals in China were prospectively included between November 2022 and December 2024. Among them, a total of 895 patients from 2 units were assigned to the training and validation sets (292 with cardia atrophy and 603 without cardia atrophy) to establish a cardia atrophy diagnostic model. 220 patients from our unit (84 with cardia atrophy and 136 without cardia atrophy) were included in the internal test set. Additionally, a total of 354 patients from 3 other units were included in the external test set (106 with cardia atrophy and 248 without cardia atrophy). In the internal and external test sets, 3 senior and 3 junior endoscopists made online diagnoses, comparing the performance differences between physicians with different levles of experience and the AI-assisted cardia atrophy detection system.

Results

This study established a AI-assisted cardia atrophy diagnostic model and tested its diagnostic performance with multicenter image data in internal and external tests. In the internal test dataset, the accuracy, sensitivity, and specificity of the AI-assisted system were 0.927, 0.941, and 0.919, respectively, with a PPV of 0.878, NPV of 0.962, and AUC of 0.967. In the external test dataset, the accuracy, sensitivity, and specificity were 0.918, 0.894, and 0.931 respectively, with a PPV of 0.874, NPV of 0.943, and AUC of 0.953. Further comparison of the diagnostic efficiency of the AI-assisted system with endoscopists of different levels of experience revealed that both in the internal and external test set, the diagnosis accuracy, sensitivity, specificity, PPV, and NPV of the AI-assisted system were all higher than those of senior endoscopists. TheAI-assisted cardia atrophy diagnostic ROC curve area (AUC) was 0.967 and 0.953 in the internal and external test sets, respectively. Heat map analysis further showed a high consistency between theAI-assisted system and endoscopists in cardia atrophy diagnosis.

Conclusion

Our newly developed AI-assisted cardia atrophy diagnostic system shows superior performance in identifying cardia atrophy compared to senior endoscopists, and can be used to guide white light endoscopic judgment and targeted biopsies for cardia atrophy.

Introduction

Piecemeal endoscopic mucosal resection (pEMR) is the preferred treatment for large non-pedunculated colorectal polyps (LNPCPs)[1,2]. A major limitation of pEMR is residual or recurrent adenoma (RRA), which was reported to in 15%-30% of cases at first surveillance colonoscopy (SC1)[3], performed 3-6 months after the index procedure, but is reduced to the range of 3%-5% by applying ablative measures to the post-EMR resection margin[4].

Aims & Methods

This study aimed to evaluate the effects of late SC1 on RRA.
This is an analysis of a prospectively collected cohort of adult patients referred for pEMR at two academic centers in Israel, from 2016 to 2023. We included all patients who underwent pEMR of LNCPCs and completed SC1.
We compared outcomes between patients who completed early SC1 at 3-6 months following the index procedure with patients who completed late SC1 later than 6 months. All procedures and surveillance colonoscopies were performed by experienced endoscopists trained in pEMR using high-definition scopes. EMR was followed by thermal ablation of the entire mucosal defect margin with snare soft tip coagulation, as previously described[4].
Scar evaluation at SC1 was performed with high-definition white light and chromoendoscopy. Our primary endpoint was RRA at SC1.
Analyses were performed per lesion. We compared baseline parameters and outcome rates between groups, and performed multivariate analysis to assess the adjusted association of months to SC1 with RRA.

Results

We analyzed 516 lesions that underwent index pEMR resection and subsequent SC1. Baseline parameters and recurrence rates are presented in Table 1. The early SC1 group (n=371) underwent SC1 at a mean of 5.1 months versus a mean of 11.1 months in the late SC1 group (p<0.01; Table 1). Polyp size in the early SC1 group was significantly larger than that in the late SC1 group (mean size 35.9 mm [SD 13.9] vs. 32.1 mm [SD 12.4], p<0.01; Table 1). The distribution of lesion location, granularity differed between the groups (Table 1). However, there were no significant differences in lesion Paris classification or rates of high grade dysplasia (Table 1).
We found no statistically significant difference in the rate of recurrence at SC1 between the two groups (6.3% in the standard group versus 4.8% in the delayed group, p=0.64). Additionally, a sub-analysis comparing the early SC1 group to patients with very late SC1 (>12 months – mean time to SC1 17.9 (SD [5.4] months) and did not reveal significant difference in recurrence at SC1 (6.2% in the early SC1 vs 6.3% in the very late group, p=1).
Multivariate analysis, adjusted for lesion size, location, and high-grade dysplasia, showed that time to SC1 was not significantly associated with RRA (odds ratio 1.05, 95% confidence interval 0.98-1.13).

TABLE 1. Comparison of baseline variables and outcome between the early and late SC1.

Conclusion

Late SC1 is not associated with an increased RRA. Hence, we suggest that high-quality pEMR with margin ablation may alleviate the need for early SC1, thereby reducing healthcare and patient burdens. Further interventional studies are required.

References

[1] Ferlitsch M, Moss A, Hassan C, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2017; 49: 270–297. doi:10.1055/S-0043-102569/ID/JR15335-1/BIB
[2] Shaukat A, Kaltenbach T, Dominitz JA, et al. Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2020; 159: 1916-1934.e2. doi:10.1053/j.gastro.2020.08.050
[3] Belderbos TDG, Leenders M, Moons LMG, et al. Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: Systematic review and meta-analysis. Endoscopy 2014; 46: 388–400. doi:10.1055/S-0034-1364970/ID/JR910-7/BIB
[4] Klein A, Tate DJ, Jayasekeran V, et al. Thermal Ablation of Mucosal Defect Margins Reduces Adenoma Recurrence After Colonic Endoscopic Mucosal Resection. Gastroenterology 2019; 156: 604-613.e3. doi:10.1053/j.gastro.2018.10.003

Disclosure

The authors report no conflict of interests

Introduction

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle has a high diagnostic accuracy and enables physicians to obtain sufficient pathological samples compared to standard needles ^1-2. However, no conclusion has been reached regarding the best combination of the number of passes and the number of to-and-fro movements (TAFs) in EUS-FNB. Although adverse events associated with EUS-FNB are rare, serious bleeding and tumor dissemination can occur ³.

Aims & Methods

Fewer passes and TAFs may help prevent these adverse events. Therefore, we conducted a prospective study to examine the diagnostic performance of a single pass with five TAFs in EUS-FNB. This single-center prospective observational study was conducted at a tertiary institution. From April 1, 2021, to August 31, 2022, 56 patients were enrolled. Three passes were performed using a 22-gauge Franseen needle (TopGain^R; Medicos Hirata, Tokyo, Japan) during the EUS-FNB. The number of TAFs were 5 in the first passes (5-TAF group) and 15 in the second and third passes (15-TAF group), respectively. Each TAF was performed with a suction technique using a 20-mL negative pressure syringe. The primary endpoint was the accuracy of the first pass, and the secondary endpoint was a qualitative comparison of the specimens between the 5-TAF and 15-TAF groups. All patients were followed up for more than 6 months. Qualitative evaluation was performed as follows: the adequate sample score ranged from 0 to 5, and the contamination and bloodiness scores ranged from 0 to 3.

Results

A total of 56 patients were enrolled in this study. Of them, data from 53 patients were analyzed. Three patients were excluded: two patients had an insufficient number of passes due to bleeding during the procedure, and one patient could not be punctured due to difficulty in identifying the lesion. The patient characteristics were as follows: median age, 73 years (range, 48–92 years), number of male patients, 28 (52.8%). The final diagnoses were malignant disease in 42 patients and benign disease in 11. The accuracy rate was 86.7% (95% confidence interval: CI, 74.7–94.5%) in the 5-TAF group, 81.1% (95% CI, 72.4–88.1%) in the 15-TAF group; the total accuracy rate in the 5-TAF and 15-TAF groups was 89.3%. There was no significant difference in the accuracy rate between 2 groups. The adequacy scores (average [standard deviation]) of the 5-TAF and 15-TAF groups were 4 [1.45] and 3.39 [1.81], respectively. The rates of adequacy scores ≥3 in the 5-TAF and 15-TAF groups were 84.9% and 72.6%, respectively (p=0.09). The contamination scores of the 5-TAF and 15-TAF groups were 1.57 [1.01] and 1.91 [1.06], respectively. The rates of contamination scores ≤1 in the 5-TAF and 15-TAF groups were 51.9% and 34.6%, respectively (p<0.05). The bloodiness scores of the 5-TAF and 15-TAF groups were 0.57 [0.64] and 0.86 [0.79], respectively. The rates of bloodiness score ≤1 in the 5-TAF and 15-TAF groups were 92.3%, and 75.0%, respectively (p<0.05). For each score, the 5-TAF group had a higher value than the 15-TAF group.

Conclusion

In the EUS-FNB with a Franseen needle, a single pass with five TAFs showed the possibility of obtaining a clinically acceptable accuracy rate and high-quality specimens.

References

1) Ishigaki K, Nakai Y, Oyama H et al. Endoscopic Ultrasound-Guided Tissue Acquisition by 22-Gauge Franseen and Standard Needles for Solid Pancreatic Lesions. Gut and Liver, 2020; 14(6): 817-825.
2) Li Z, Liu W, Xu X et al. A Meta-Analysis Comparing Endoscopic Ultrasound-guided Fine-needle Aspiration With Endoscopic Ultrasound-guided Fine-needle Biopsy. J Clin Gastroenterol 2022; 56(8): 668-678.
3) Mizuide M, Ryozawa S, Fujita A, et al. Complications of endoscopic ultrasound-guided fine needle aspiration: a narrative review. Diagnostics (Basel). 2020; 10: 964.

Disclosure

The authors have no conflicts of interest directly relevant to the content of this article.

Clinical Case Summary

Introduction: Locally advanced pancreatic tumors can lead to both biliary and duodenal obstruction by invasion or compression. Quality of life is severely affected if obstruction occurs: jaundice, emesis and pain can become invalidating and patients become too frail for palliative chemotherapy and are sometimes declared unfit even for derivative surgery. Recently, endoscopic techniques under EUS or ERCP guidance are being used to create biliodigestive and enteral anastomoses.
Clinical case: A 75-year-old female was diagnosed with locally advanced pancreatic head adenocarcinoma in January 2024. The tumor was declared unresectable and chemotherapy was initiated. A plastic stent was inserted into the main biliary duct (MBD) to ensure biliary drainage. In May 2024, she presented with cholangitis and emesis. EGD revealed duodenal stenosis and ERCP failed due to tumor infiltration. A combined endoscopic approach was performed: EUS-guided hepatico-gastrostomy (EHG) for biliary drainage and EUS-guided gastro-enterostomy using a lumen-apposing metal stent (LAMS). In July 2024, the plastic stent was removed, and in August 2024, two fully covered 60 x 10 mm SEMS were inserted antegrade through the EHG into the MBD to improve patency. At 11 months post-intervention, the patient returned for routine reassessment, declaring good clinical performance: she remained asymptomatic, with routine blood tests, including bilirubin levels within normal range and with all stents patent and correctly positioned (confirmed radiologically and endoscopically). The patient was able to maintain oral intake and continue chemotherapy. No late adverse events were noted.
Conclusion: This case demonstrates the long-term clinical and technical success of a staged endoscopic triple bypass for the management of complex biliary and duodenal obstruction due to unresectable pancreatic cancer. The approach was minimally invasive, well tolerated and remarkably improved the patient's quality of life.

References

1. Adler, Douglas G MD; Baron, Todd H MD, FACP. Endoscopic Palliation of Malignant Gastric Outlet Obstruction Using Self-Expanding Metal Stents: Experience in 36 Patients. American Journal of Gastroenterology 97(1):p 72-78, January 2002. | DOI: 10.1111/j.1572-0241.2002.05423.x
2. Giovannini, Marc. (2019). EUS-guided hepaticogastrostomy. Endoscopic Ultrasound. 8. 35. 10.4103/eus.eus_47_19.
3. Dumonceau, Jean-Marc & Tringali, Andrea & Blero, Daniel & Devière, J & Laugiers, R & Heresbach, D & Costamagna, Guido. (2012). Biliary stenting: Indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy. 44. 277-98. 10.1055/s-0031-1291633.
4. Van Der Merwe, S. W., Van Wanrooij, R. L., Bronswijk, M., Everett, S., Lakhtakia, S., Rimbas, M., ... & Van Hooft, J. E. (2022). Therapeutic endoscopic ultrasound: European society of gastrointestinal endoscopy (ESGE) guideline. Endoscopy, 54(02), 185-205. 10.1055/a-1717-1391