Introduction

As curative criteria of undifferentiated-type gastric cancer (UD-GC) by endoscopic submucosal dissection (ESD), it is defined lesions fulfill the pathological size ≤ 20 mm, pT1a, absence of ulcerative findings (UL-0), absence of lympho-vascular invasion (LVI-0) and R0 resection in Japanese gastric cancer treatment guidelines. However, additional gastrectomy is needed for other UD-GCs. Meanwhile, it is reported that pathological size of ≤ 40 mm, pT1a, purely UD-GC (without differentiated-type [D-type] components) patients with UL-0 and LVI-0 did not show lymph node metastasis (LNM). Additionally, it is reported that no LNM occurred in the patients with pathological size > 20 mm, pT1a, UD-GC, UL0, LVI-0, and retained double-layer structure (as distribution of cancers in mucosa, the upper layer primarily comprises intracytoplasmic abundant mucin with an eccentric nucleus, and the lower layer primarily comprises poor intracytoplasmic mucin and acidophilic cytoplasm). However, all of these studies were single-center retrospective studies with a small sample size of surgical cases, and there have been no multi-institutional studies with central pathological review (CPR).

Aims & Methods

This was a multicenter retrospective study from 45 Japanese institutions to determine the proportion of LNM, and clarify the clinicopathological characteristics of the lesions without LNM (as no metastasis of lymph nodes in surgical specimens). We included patients pathologically diagnosed with purely UD-GC, lesion size 21-40 mm, pT1a, UL0, LVI-0 by initial gastrectomy or gastrectomy after ESD at each institution. Patient information was entered into an electronic case report form via electronic data capture. In addition, seven unstained slides, including the deepest invasive area of each lesion, were collected from each institution, and hematoxylin-eosin staining and immunostaining for MUC5AC and MUC6 were performed. As a CPR, two pathologists assessed whether UL-0, pT1a, and absence of minor tubular components (as a small amount of tubular components) were observed. UL-1, pT1b, D-type dominance or unevaluable specimens were excluded. Further, whether the lesion involved the entire mucosal layer and whether a double-layer structure was present. The final decision on the lesions with discrepancies was made through discussion with another member of the CPR via web meeting.

Results

Of the 652 patients enrolled, 127 were excluded due to UL-1, pT1b, D-type dominance or unevaluable specimens by the CPR. In 525 eligible patients (initial gastrectomy; 444, gastrectomy after ESD; 81), 10 patients had LNM (1.8%, 95% Confidence Interval [CI] 0.9-3.5%). Comparing 10 patients in the LNM group with 515 patients in the non-LNM group, there were no significant differences in the pre-treatment endoscopic findings. Meanwhile, the results of the CPR revealed that the absence of minor tubular components is more frequent in the non-LNM group than that in the LNM group (365/515, 70.9% vs 3/10, 30%, p=0.011). When stratified by the results of the CPR, patients with preserved double-layer structure did not have LNM (0/41, 95%CI 0-8.6%). Meanwhile, patients without minor tubular components had 0.8% as proportion of LNM, and upper of 95%CI was low among each population (3/365, 95%CI 0.2-2.4%).

Conclusion

There were 1.8% of LNM in all eligible patients. In contrast, as purely UD-GC, lesion size 21-40 mm, pT1a, UL0, LVI-0 without minor tubular components had a low proportion of LNM, they are promising candidates for the expansion as the curative criteria of ESD.

Introduction

Histopathology remains the gold standard for the assessment of diminutive (≤5 mm) colorectal polyps, but it requires considerable cost and resources allocation. Optical diagnosis supported by artificial intelligence (AI) has shown promise, though its integration into clinical decision-making is limited. Our prior work showed the feasibility of replacing histopathology with AI-assisted human optical diagnosis in real-time practice.¹

Aims & Methods

This study aimed to assess patient acceptance, and diagnostic performance of autonomous computer-aided optical diagnosis (CADx) when used as the sole determinant in resect-and-discard (RD) and diagnose-and-leave (DL) strategies.
This prospective study was conducted at the University of Montreal Hospital Center between August and November 2024 (ID: CER23.095, NCT06059378). Consecutive patients aged 45–80 years undergoing elective colonoscopy were approached and provided detailed information about the use of CADx, and the principles of the RD and DL strategies. For consented patients, procedures were performed using CADEYE system, which autonomously provided an optical diagnosis for detected diminutive polyps. Lesions predicted to be neoplastic were removed and discarded without histopathologic analysis (RD), while rectosigmoid lesions predicted to be hyperplastic were left in place (DL). All colonoscopies were video-recorded. To establish the reference standard, the videos of all polyps undergoing optical diagnosis were independently reviewed by two expert endoscopists. In cases of disagreement, a third reviewer arbitrated the final decision. The primary outcome was the proportion of patients consenting to undergo autonomous CADx. Secondary outcomes included the accuracy of the RD strategy, the negative predictive value (NPV) of the DL approach, and the agreement between CADx- and expert-driven surveillance interval recommendations.

Results

95/102 patients approached (93.1%) consented to undergo CADx-based optical diagnosis (mean age 65.7 years). Among 149 diminutive polyps detected (51 (34.2%) in the rectosigmoid and 98 (65.8%) in the proximal colon), CADx provided optical diagnosis in 98.7% (n=147) of cases. The RD and DL strategies were applied to 113 (76.9%) and 30 (20.4%) of polyps, respectively. After excluding indeterminate cases (n=5) and sessile serrated lesions (SSLs) (n=14), the RD strategy achieved an accuracy of 83.5% and the DL strategy demonstrated a NPV of 92.3%. Surveillance interval agreement between CADx and expert recommendations was 100% (95%CI 96.2-100.0). Sensitivity analyses showed reduced performance when SSLs were classified as neoplastic, but Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) benchmarks were met when SSLs were considered hyperplastic.

Table 1. Diagnostic performance of computer- assisted optical diagnosis (CADx), using expert optical diagnosis as the reference.

Diagnostic performance (%; (95% CI))	Sensitivity	Specificity	PPV	NPV	Accuracy
RD	77.6% (65.78-86.89)	96.7% (82.78-99.92)	98.1% (86.29-99.72)	65.9% (55.19-75.21)	83.5% (74.60-90.27)
DL	-	96.0% (79.65-99.90)	-	92.3% (91.72-92.86)	88.9% (70.84-97.65)

RD: resect and discard; DL: diagnose and leave; NPV: negative predictive value; PPV: positive predictive value; CI: confidence interval.

Conclusion

Autonomous CADx achieved high patient acceptance and met key performance benchmarks for managing diminutive polyps using RD and DL strategies. These findings support its potential for safe, real-world implementation, though further development is needed to address current limitations in SSL detection and to enable quality optical diagnosis practice.

References

1. Taghiakbari M, Rex DK, Pohl H, et al. Pragmatic Resect and Discard Implementation Using Computer-Assisted Optical Polyp Diagnosis. Gastroenterology 2025;168:154-156.e2.

Disclosure

Daniel von Renteln has received research funding from ERBE Elektromedizin GmbH, Ventage, Pendopharm, Fujifilm and Pentax, and has received consultant or speaker fees from Boston Scientific Inc., ERBE Elektromedizin GmbH, and Pendopharm. Roupen Djinbachian has received speaker fees from Fujifilm. The remaining authors declare that they have no conflict of interest.

Introduction

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease affecting the biliary epithelium, leading to bile duct strictures and eventually cirrhosis. Liver fibrosis is a well-established predictor of disease outcome in PSC. The Enhanced Liver Fibrosis (ELF) test, which combines three direct serum markers—hyaluronic acid (HA), tissue inhibitor of metalloproteinases-1 (TIMP-1), and amino-terminal pro-peptide of type III pro-collagen (PIIINP)—has been shown to correlate with the Ishak staging of liver histology in PSC. Both the ELF score and its individual components demonstrate moderate diagnostic accuracy in distinguishing advanced fibrosis (AUROC 0.73–0.78) and cirrhosis (AUROC 0.73–0.81) [1].
However, liver fibrosis and cirrhosis in PSC develop as secondary consequences of bile duct strictures and therefore represent late-stage indicators of disease progression. We have previously shown that biliary levels of calprotectin and interleukin-8 (IL-8) can help identify patients at higher risk of developing bile duct strictures. Moreover, our findings indicated that commonly used liver function tests, particularly plasma alkaline phosphatase (P-ALP), lack both sensitivity and specificity for effectively monitoring PSC progression [2].

Aims & Methods

To study: 1) the association of ELF with ERC-score, 2) the predictive value of ELF for bile duct disease progressio assessed by ≥2 increase in ERC score or need for dilatation, 3) the role of ELF-test to predict the overall disease outcome.
We included patients from Helsinki PSC-registry with ELF determined at least once, and ≥2 ERC examinations. End of f/u was 31.12.23. ERC -score was determined as described earlier [3]. ELF ≥9.8 was used as a marker for advanced liver fibrosis.

Results

In total, we included 397 patients. Demographics, laboratory results, and outcomes stratified by ELF levels, are presented in the table. Increase of ERC-score did not differ between groups, but the score at baseline associated with ELF-test (p<0.001). Progression of PSC assessed by increase of ERC score≥2 or dilatation did not correlated with ELF-levels (p=0.11), but ln[P-hyaluronic acid] showed close association with progression of bile duct changes (p<0.001). The probability for LTx increased in a linear way with the increase of ELF-level. (<0.001).

Variables	ELF ≤9.8 N=310	ELF 9.8-11.2 N=62	ELF ≥11.3 N=25	p for linearity
Person years. [Median (IQR) of person years]	2181 [5.6(3.5,11.8)]	414 [5.6(3.5,11.8)]	82 [2.5(1.3,3.8)]	-
PSC duration, mean (SD), years	6.9(5.8)	8.8(6.0)	11.2(8.1)	<0.001
AOM, mean (SD)	1.39(0.46)	1.83(0.56)	2.49(0.67)	<0.001
P-ALP, U/l, median (IQR)	94(74,135)	168(107,250)	317(203,438)	<0.001
P-Bil, µmol/l, median (IQR)	11(8,17)	13(9,18)	29(17,48)	<0.001
Biliary calprotectin, mg/l, median (IQR)	1.3(0.2,15.8)	13.4(0.9,71.0)	22.4(9.1,133.0)	<0.001
Increase of ERC score ≥2, n(%)*	35(11)	9(15)	4(16)	0.35
Increase of ERC score≥2 or dilatation, n(%)*	142(46)	40(65)	20(80)	<0.001
CCA, HCC, GBCA, Death, LTx (Incidence (95% CI), [no])**	15(10 to 21), [32]	60(39 to 89), [25]	220(30 to 347), [18]	<0.001

* Adjusted linearity for age, sex, PSC duration, intra-and extrahepatic disease,and ERC-score at baseline
** per 1000 pyrs. Adjusted for age, sex, PSC duration, intra-and extrahepatic disease.
Abbreviations: AOM, Amsterdam-Oxford model; CCA, cholangiocarcinoma, GB-CA, gallbladder carcinoma; LTx, liver transplantation.

Conclusion

The ELF test correlates with the severity of bile duct disease and the risk of liver transplantation, but it is not suitable for assessing the progression of bile duct changes based on sequential ERC examinations. The role of hyaluronic acid as a surrogate marker of bile duct changes deserves further studies.

References

[1] Thorburn DT et al. Hepatology Communications 2024;8(7):e0467, [2] Färkkilä M et al. JHEP Rep. 2024 Jul 2;6(10):101161, [3] Boyd S, et al. Endoscopy. 2016;48:432-9.