Introduction

Lynch syndrome (LS) is the most frequent hereditary cancer syndrome, responsible for 3-5% of all colorectal cancer (CRC) cases. Patients with LS are at increased risk for metachronous CRC, influenced by the specific gene involved and the extent of prior surgical intervention¹. However, the impact of colonoscopy surveillance on metachronous CRC incidence in LS carriers has not been clearly defined.

Aims & Methods

To characterize LS carriers at risk of developing metachronous CRC based on the affected gene and the extent of prior surgery. To describe follow-up characteristics, particularly the rate of colonoscopy surveillance. To report the incidence of metachronous CRC according to surgical extent and gene mutation. To analyze potential risk factors associated with metachronous CRC development.
This retrospective multicenter study included 583 LS carriers diagnosed with CRC; 43 were excluded due to missing surgical or follow-up data, resulting in 540 patients analyzed. Patients were categorized by high-risk genes (MLH1, MSH2) or low-risk genes (MSH6, PMS2) and by surgical extent (extensive or partial colectomy). Colonoscopy surveillance was defined as at least one colonoscopy following the initial CRC diagnosis or between successive CRC events in cases of metachronous CRC. Survival analysis assessed the incidence of metachronous CRC.

Results

Among the 540 included carriers, 247 (45.7%) had MLH1 mutations, 181 (33.5%) MSH2, 80 (14.8%) MSH6, and 32 (5.9%) PMS2. Participants were grouped into four categories: high-risk/extensive colectomy (N=58), high-risk/partial colectomy (N=370), low-risk/extensive colectomy (N=9), and low-risk/partial colectomy (N=103). Age at first CRC diagnosis was significantly higher in high-risk groups compared to low-risk groups. No differences were found between groups regarding sex, tumor location, or tumor stage. Median follow-up duration was 8.6 years (IQR 4.5-14.6), with no significant differences among groups. During follow-up, 107 cases of metachronous CRC occurred. Survival analysis revealed significant differences in metachronous CRC incidence (Log-rank test: p=0.006), with 10-year incidence rates of 6.4% for high-risk/extensive colectomy, 17.9% for high-risk/partial colectomy, 0% for low-risk/extensive colectomy, and 4.8% for low-risk/partial colectomy groups. Risk factors significantly associated with metachronous CRC included high-risk gene mutations (HR 2.49, 95% CI 1.2-4.77) and initial CRC diagnosis before the year 2000 (HR 1.61, 95% CI 1.02-2.55). Colonoscopy surveillance was associated with a reduced risk of metacronous CRC (HR 0.06, 95% CI 0.04-0.09).

Table 3. Metachronous CRC risk factors

Conclusion

Individuals carrying pathogenic variants in MLH1 or MSH2 who undergo partial colectomy face a markedly increased risk of developing metachronous CRC. Nonetheless, the introduction of structured colonoscopic surveillance and optimized management strategies after the year 2000 has significantly mitigated this risk. These findings are essential for informing surgical decision-making in patients with LS and CRC, particularly when evaluating the most appropriate extent of colectomy.

References

Eikenboom EL, Moen S, Van Leerdam ME, Papageorgiou G, Doukas M, Tanis PJ, et al. Metachronous colorectal cancer risk according to Lynch syndrome pathogenic variant after extensive versus partial colectomy in the Netherlands: a retrospective cohort study. The Lancet Gastroenterology & Hepatology. 2023 Dec;8(12):1106–17.

Introduction

Malignant biliary obstruction (MBO) caused by non-hepatobiliary-pancreatic (non-HBP) malignancies is a rare and underexplored indication for endoscopic retrograde cholangiopancreatography (ERCP). These cases often present a clinical dilemma: while ERCP offers a minimally invasive option, its utility remains uncertain in patients with poor prognosis and advanced disease.

Aims & Methods

We aimed to evaluate the effectiveness of ERCP-guided biliary drainage in this context and identify baseline predictors of clinical failure to help refine patient selection.
We conducted a retrospective analysis of all patients who underwent ERCP for malignant biliary obstruction of non-HBP origin between March 2018 and February 2025. Patients lacking essential clinical or follow-up data were excluded. Technical success was defined as adequate stent placement; clinical success as a ≥50% reduction in bilirubin or resolution of cholangitis within 2 weeks. The predictive role of bilirubin level, stricture location, serum albumin, and ECOG performance status was assessed. A ROC analysis evaluated the discriminative ability of pre-drainage bilirubin.

Results

Forty-eight patients were included (mean age: 55.6 years; 56% women). The most common primary cancers were colorectal (31%, n=15), gastric (18%, n=9), breast (14%, n=7), lung (10%, n=5), and ovarian (8%, n=4). Hilar strictures were observed in 54% (n=26) and mid-to-distal strictures in 46% (n=22). All procedures were performed using plastic stents. In most cases involving hilar strictures, long stents (e.g., 7 Fr / 12–15 cm) were used, and a single biliary sector—usually the most dilated or invaded—was preferentially drained. Technical success was achieved in 85.4% of cases. Clinical success occurred in 54.1% of patients, while early mortality (≤30 days) reached 10.4%, exclusively among individuals with ECOG status 4 and serum albumin <2.8 g/dL. Hilar strictures and total bilirubin levels >200 mg/L were significantly associated with lower clinical success rates (38% vs 65%, p=0.03 and 33% vs 62%, p=0.04, respectively). ROC analysis showed an AUC of 0.72 for bilirubin in predicting failure. Technical failures (14.6%) were mainly due to anatomical distortion or papillary inaccessibility.

Conclusion

Endoscopic biliary drainage in this population is technically achievable but offers limited clinical benefit, especially in cases with hilar involvement, severe hyperbilirubinemia, or poor overall condition. These findings emphasize the importance of using simple, baseline clinical indicators to guide treatment decisions, avoid unnecessary interventions, and adapt care strategies to the realities of resource-limited settings.

Disclosure

I have no conflict of interest.

Introduction

Accurate prediction of lymph node metastasis (LNM) in submucosal invasive (T1) colorectal cancer (CRC) is essential for determining the need for additional surgery following endoscopic resection. Conventional histopathological assessments, however, are limited by interobserver variability. This study aimed to develop and externally validate a stacking-based artificial intelligence (AI) model integrating histopathological whole slide images (WSIs) and clinical parameters to predict the risk of LNM in T1 CRC.

Aims & Methods

This retrospective study included 1,056 patients with histologically confirmed T1 CRC treated at Showa Medical University Northern Yokohama Hospital. Of these, 593 cases were used for model training and 100 for internal testing. External validation was conducted on 25 cases from two independent institutions.
The proposed stacking ensemble model incorporated the Multiple Instance Self-Training (MIST) score derived from WSIs, patient sex, and tumor location (colon vs. rectum). Base learners included logistic regression, XGBoost, and random forest, with a meta-learner synthesizing their outputs to generate the final LNM prediction. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) in both internal and external cohorts.

Results

LNM was observed in 69 (11.6%) training cases, 15 (15.0%) test cases, and 2 (8.0%) external validation cases. The model achieved an AUC of 0.6965 in the internal test cohort and 0.7500 in the external validation cohort, demonstrating stable and generalizable predictive performance.
A representative case involved a 64-year-old man with a 16-mm type 0-Is lesion in the sigmoid colon resected via endoscopic mucosal resection (EMR). Histopathology showed well-differentiated tubular adenocarcinoma (tub1 > tub2), submucosal invasion depth of 3,300 µm (T1b), tumor budding grade BD1, Ly0, V1a, and negative resection margins (HM0, VM0). Despite guideline-based recommendations prompting additional surgical resection, no LNM was found (N0, 0/16), and the patient remained recurrence-free five years postoperatively—consistent with the AI model’s prediction.

Conclusion

The stacking-based AI model exhibited robust and generalizable performance in predicting LNM in T1 CRC, both internally and across external institutions. This approach offers a complementary tool to conventional pathology and may enhance individualized decision-making regarding the necessity of additional surgical intervention.

Introduction

Currently, there is no established treatment strategy for obstructive unresectable colorectal cancer (OUCC). The European Society of Gastrointestinal Endoscopy guidelines suggest that colonic self-expandable metallic stent (SEMS) followed by chemotherapy can be safely performed, but Japanese guidelines suggested negative recommendation due to risk of SEMS-related complications. However, colonic SEMS has the advantage of early introduction of chemotherapy compared to other decompression methods, and avoidance of stoma creation, but its safety and efficacy are globally unknown.

Aims & Methods

Patients diagnosed with OUCC at initial presentation from April 2012 to December 2022, implanted with a SEMS, and introduced systemic chemotherapy within 3 months after implantation were included. The endpoints of this study were perforation during SEMS implantation and progression-free survival (PFS).

Results

A total of 302 patients were included from 26 centers, and 289 patients were included in the final analysis. The median age was 68 years, 59.2% were male, 10.7% had PS2-3, 11.1% had more than 3 metastatic organs, and 46.7% had RAS-mutated. Anti-EGFR antibody drugs were used in 30.8% and Bevacizumab in 19.0% of patients in 1^st line therapy. The time from implantation to the start of chemotherapy was 11 (IQR: 6-21days). The cumulative perforation rate was 8.7% and the median time of occurrence was 144 days. The perforation rate with Bevacizumab usage was higher, but the difference was not statistically significant (14.5% vs 7.3%, P=0.107). Anti-EGFR antibody usage was not statistically associated with SEMS-related complications. The response rate was 57.9%. Primary resection was performed in 34.9% of patients, and the time to resection was 129 days. Median PFS was 9.2 months. Univariate analysis showed significant differences in PFS for age, number of metastatic organs, perforation, Triplet regimen, anti-EGFR antibody, primary tumor resection, and colostomy, and independent prognostic factors in the Cox proportional hazards model were number of metastatic organs (≥3: HR 1.63, 95% CI 1.08-2.47), perforation (HR 1.72, 95% CI 1.10-2.69), and no primary resection (HR 4.22, 95% CI 2.88-6.20).

Conclusion

Obstruction itself is a poor prognostic factor, and patients with OUCC may tolerate treatment less well than non‑obstructed patients, particularly when angiogenesis inhibitors are difficult to use. Within this context, the efficacy of post‑SEMS chemotherapy in our cohort appears acceptable. However, given the relatively high perforation rate, early resection of the primary tumor should be considered in patients expected to continue and benefit from systemic therapy.

Introduction

The lymphocyte-to-monocyte ratio (LMR) is widely utilized as a surrogate marker of systemic inflammation and is increasingly recognized as an indicator of immune status within the tumor microenvironment, particularly in the setting of cancer immunotherapy.

Aims & Methods

^​​​​​This study aimed to evaluate the prognostic relevance of LMR in patients undergoing combination therapy with durvalumab (Dur) and tremelimumab (Tre) for unresectable hepatocellular carcinoma (uHCC). A total of 242 patients with uHCC who received Dur/Tre therapy at multiple institutions between February 2023 and March 2025 were retrospectively analyzed. Inclusion criteria encompassed available baseline LMR, Child-Pugh class A liver function, and complete clinical data. Patient characteristics were as follows: median age 74.0 years (IQR: 68.3–77.0); sex distribution, 202 males and 40 females; performance status (PS) 0/1/≥2: 201/32/9; underlying liver disease (HBV/HCV/HBV+HCV/NBNC): 37/72/1/132; BCLC stage (≤A/B/≥C): 19/68/155; Child-Pugh score (5/6): 125/117; alpha-fetoprotein (AFP) level: 57.6 ng/mL (IQR: 4.3–909.8); LMR: 3.14 (2.18–4.15); treatment line (first-/second-line): 94/148; and median observation period: 9.0 months (5.0–14.2).

Results

The median progression-free survival (PFS) and overall survival (OS) were 3.5 months (2.8–4.3) and 19.2 months (15.4–NA), respectively. Time-dependent ROC analysis identified 2.15 as the optimal LMR cutoff at 25% of the observation period (15.4 months). Objective response rates per RECIST version 1.1 were as follows: complete response (CR), 3.2%; partial response (PR), 15.5%; stable disease (SD), 32.4%; and progressive disease (PD), 48.9%. Disease control rate (DCR) was significantly higher in the LMR ≥2.15 group compared to the <2.15 group (55.4% vs. 37.3%, p = 0.026). Patients with LMR ≥2.15 demonstrated significantly longer PFS (3.8 months [95% CI: 3.8–4.6] vs. 2.7 months [95% CI: 2.00–4.00]; p= 0.005) and OS (NA months [95% CI NA: –17.9] vs. 13.2 months [95% CI: 8.5–17.1]; p = 0.005). In multivariate analysis using the Cox proportional hazards model, LMR ≥2.15 emerged as an independent predictor of both PFS (HR = 0.622; 95% CI: 0.438–0.884; p = 0.008) and OS (HR = 0.558; 95% CI: 0.328–0.949; p = 0.031). Hazard ratio approximation curves indicated that the range of LMR associated with significant prognostic impact on both PFS and OS was approximately 1.6 to 2.4. Subgroup analysis further demonstrated that in first-line treatment settings, patients with LMR ≥2.15 had superior PFS and OS outcomes compared to those with LMR <2.15 (PFS: p = 0.028; OS: p = 0.016).

Conclusion

​​​​LMR serves as a valuable prognostic biomarker in patients receiving Dur/Tre combination therapy for uHCC, with potential utility in guiding therapeutic decision-making.

Disclosure

Toshifumi Tada: lecture fees from AbbVie, Eisai, and Chugai
Atsushi Hiraoka: lecture fees from Eisai, Bayer, Eli Lilly, and Otsuka
Hidenori Toyoda: lecture fees from AbbVie, Eisai, Gilead, Terumo, and Bayer

Introduction

The management of malignant hilar biliary obstruction can be done by endoscopic biliary stenting, which is a well-established palliative treatment, improving the quality of life by relieving symptoms.

Aims & Methods

This systematic review and meta-analysis aimed to compare the use of stents placed above and across the sphincter of Oddi in patients with malignant hilar biliary obstruction. We performed a systematic search of the PubMed, Embase, and Cochrane Library databases in April 2025. Article screening was conducted independently by two authors using Rayyan software. Inclusion criteria were randomized controlled trials (RCTs) comparing stent placement above and across the sphincter of Oddi for malignant hilar biliary obstruction, evaluating at least one of the outcomes of interest. The outcomes were stent migration, stent patency, cholangitis, stent occlusion, and successful placement of the stent. RStudio software was used for statistical analysis, applying a random-effects model to calculate the risk ratio (RR) in binary outcomes and mean differences (MD) in continuous outcomes.

Results

We included three RCTs comprising 161 patients. There was no significant difference between the transpapillary and suprapapillary stents regarding the rates of stent migration (RR 2.03; 95% CI 0.41–10.16; p=0.39; I²=55%), cholangitis (RR 0.65; 95% CI 0.08–5.07; p=0.68; I²=0%), technical success (RR 0.99; 95% CI 0.95–1.04; p=0.80; I²=0%), and stent occlusion (MD 89.20; 95% CI 16.30–162.10; p=0.02; I²=78%). However, the mean number of patent stents was significantly lower in the suprapapillary stent group.

Conclusion

The two types of stent seem similar in terms of technique, efficacy, and safety, although the suprapapillary stent seems superior in terms of stent patency.

References

Ko SW, Joo HD, Song TJ, Kim S, Choi SJ, Oh CH, Oh D, Park JS, Yoon SB, Yoon JH, Seo DW, Lee SK. Impact of the suprapapillary method on patency in distal malignant biliary obstruction: a multicenter randomized controlled trial. Gastrointest Endosc. 2024 Oct;100(4):679-687.e1. doi: 10.1016/j.gie.2024.03.024. Epub 2024 Mar 21. PMID: 38521477.
Kurita A, Uza N, Asada M, Yoshimura K, Takemura T, Yazumi S, Kodama Y, Seno H. Stent placement above the sphincter of Oddi is a useful option for patients with inoperable malignant hilar biliary obstruction. Surg Endosc. 2022 May;36(5):2869-2878. doi: 10.1007/s00464-021-08576-x. Epub 2021 Jun 2. PMID: 34076770.
Finn Møller Pedersen, MD, Annmarie Touborg Lassen, Ove B. Schaffalitzky de Muckadell. Finn Møller Pedersen, MD, Annmarie Touborg Lassen, Ove B. Schaffalitzky de Muckadell. Gastroint Endosc. 1998;48(6):574-579.

Introduction

In the carcinogenic pathway of colorectal cancer, the first concept is the "adenoma-carcinoma sequence" and the second concept is the " serrated pathway ". In these concepts, adenomas and serrated lesions gradually progress to cancer. The third concept is the "de novo pathway," in which cancer develops without adenomas or serrated lesions and is also characterized by high malignancy and rapid progression. We have endoscopically characterized depressed colorectal cancers considered to be of the "de novo pathway" and validated the usefulness of pit pattern and EC classification.

Aims & Methods

A total of 54819 colorectal neoplasms were resected endoscopically or surgically in our institution from April 2001 to December 2024. They were subjects of this study. Advanced cancers were excluded. Of these, 1694 lesions were submucosally invasive (T1) carcinomas, 7330 lesions were classified as high-grade dysplasia and 39977 lesions as low-grade dysplasia. Morphologically, they were divided into 3 types: depressed, flat, and protruded type comprising 1.0 (%), 46.4 (%),and 52.6（%), respectively. Specifically, the distinctive features of depressed type neoplasms concerning their pit pattern and EC classification were examined. EC classification is a classification for an endocytoscopy that can evaluate pathology, such as nuclear atypia and glandular structure, by magnifying stained cells. EC1a is diagnosed as normal mucosa, EC1b is diagnosed as hyperplastic polyps, and if slit-like glandular ducts or spindle-shaped nuclei are present, it is classified as EC2 and diagnosed as an adenoma or intramucosal carcinoma. If irregularly shaped glandular ducts or nuclei with a high N/C ratio are found, it is classified as EC3a, and diagnosed as intramucosal carcinoma or SM lightly invasive carcinoma. If the glandular ducts are indistinct and the nucleus is irregularly shaped and darkly stained, it is classified as EC3b and diagnosed as SM highly invasive carcinoma.

Results

Most of the flat (91.5%) and protruded type (94.9%) lesions showed type IIIL or IV pit pattern, which are common findings in adenomas. On the other hand, most of the depressed type lesions (92.6%) classified as type IIIs, VI or VN pit patterns, are typically seen in carcinomas. As for endocytoscopy, most of flat and protruded type lesions were identified as EC2 corresponding to adenomas. In contrast, relatively high rates of depressed type lesions were categorized as EC3a (40.3%) and EC3b (52.4%), consistent with invasive carcinomas.
The proportion of T1 carcinomas in depressed type lesions was 58.7%, whereas in flat and protruded type lesions it was 2.5% and 2.5%, respectively. Additionally, 12.0% of depressed type lesions less than 5mm in diameter were T1 carcinomas, whereas flat and protruded type lesions were 0.01% and 0%, respectively.

Conclusion

This study revealed that depressed lesions were classified as type IIIs, VI or VN pit patterns on magnifying endoscopy and as type EC3a or EC3b on endocytoscopy. Lesions with these features or pit patterns tend to invade the submucosal layer even if they are small size. Despite their high potential for malignancy, depressed lesions are often ignored. However, it is critical to recognize their features and accurately diagnose lesions based on morphology, pit pattern, and EC classification.

Disclosure

Shin-ei Kudo and Masashi Misawa received speaking honoraria from Olympus Corporation and have an ownership interest of the products of Cybernet Systems. Tetsuo Nemoto received a research grant from Olympus Corporation for other studies. Other authors have nothing to declare.