Introduction

Systemic therapy for unresectable hepatocellular carcinoma (HCC) has increasingly incorporated immune checkpoint inhibitors (ICIs) as the standard of care in recent years. Among them, the combination of atezolizumab and bevacizumab (Atezo/Bev) has demonstrated high efficacy as a first-line therapy. In pursuit of improved outcomes, therapeutic strategies combining systemic and locoregional treatments have gained attention.

Aims & Methods

This study aimed to evaluate whether combining cisplatin-based hepatic arterial infusion chemotherapy (HAIC) with Atezo/Bev could enhance treatment efficacy and safety compared to Atezo/Bev alone.
This was a multicenter, open-label, randomized controlled trial (jRCTs061210065). Patients diagnosed with unresectable HCC who met the eligibility criteria were randomized into two groups: (1) Atezo/Bev alone (control group) and (2) Atezo/Bev plus HAIC (intervention group). The primary endpoint was objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), disease control rate (DCR), and safety.

Results

A total of 71 patients were enrolled, with 67 included in the efficacy and safety analyses after excluding dropouts (control: n=34, intervention: n=33). Baseline characteristics were well balanced between groups: median age 74 vs. 74 years, male 79.4% vs. 87.9%, viral hepatitis 29.4% vs. 30.3%, ALBI score -2.21 vs. -2.14, macrovascular invasion 17.6% vs. 15.1%, extrahepatic spread 20.0% vs. 17.9%, and prior TACE history 32.4% vs. 33.3%.
The ORR was 28.0% (7/25) in the control group and 52.2% (12/23) in the intervention group. The DCR was 68.0% (17/25) vs. 82.6% (19/23), respectively. The incidence of adverse events was comparable between groups (59.3% vs. 60.0%), and all events were consistent with known profiles.

Conclusion

This trial evaluated the addition of cisplatin-based HAIC to an ICI-based regimen for HCC. While cisplatin is widely used as a key drug in the treatment of solid tumors, it is not commonly adopted for HCC outside Japan. In Japan, however, HAIC using cisplatin has shown promising efficacy in phase I/II trials and has been widely implemented. Although long-term outcomes require further investigation, this study demonstrated that combining HAIC with Atezo/Bev may lead to improved treatment efficacy, warranting further attention and validation.

References

None

Disclosure

Nippon Kayaku Co.,Ltd.

Introduction

Spontaneous bacterial peritonitis (SBP) is a well-recognized decompensation that significantly affects the clinical outcome of patients with liver cirrhosis. The aim of this study is to assess the factors associated with short-term mortality in this patient population.

Aims & Methods

We conducted a retrospective study (January 2022 to December 2024) on all cirrhotic patients with SBP, admitted in the Gastroenterology Department of “St. Spiridon” County Clinical Emergency Hospital Iasi, a tertiary referral center. The SBP cases were identified based on elevated ascitic fluid absolute PMN count > 250 cells/mm³, with or without positive ascitic fluid bacterial culture.

Results

Out of the 114 cirrhotic patients diagnosed with SBP for the first time, 39 (34,2%) were female and 75 (65,8%) were male, with a mean age of 57 years. Most patients had advanced liver disease according to the Child-Pugh classification: 98 patients (86%) were classified as Child C, and 16 patients (14%) as Child B. The mean MELD-Na score was 23.3 points. The overall in-hospital mortality rate was 17.5% (20 patients). According to the multivariable analysis, several factors were significantly associated with in-hospital mortality, such as: renal dysfunction (OR 8.4118 [95% CI 2.9190 to 24.2403]; P=0.0001), serum bilirubin higher than 3 mg/dl (OR 4.8571 [95% CI 1.7445 to 13.5216]; P=0.0025), serum sodium lower than 130 mmol/l (OR 4.3750 [95% CI 1.5973 to 11.9833]; P=0.0041), international normalized ration (INR) higher than 2 (OR 4.5222 [95% CI 1.6471 to 12.4161]; P=0.0034).

Conclusion

Renal dysfunction, elevated INR, hyperbilirubinemia, and hyponatremia appear to be significant factors associated with the worsening of prognosis in cirrhotic patients with SBP, influencing in-hospital mortality.

Introduction

Endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (SESCC) involving the entire circumference carries the extremely high risk of stricture and also raises concerns about curative resection. Therefore, the current Japanese guidelines weakly recommend ESD only for circumferential SESCCs diagnosed as cEP/LPM and sized ≤ 50 mm, while surgery or chemoradiotherapy (CRT) is recommended for circumferential SESCCs other than the above. ¹ However, in clinical practice, ESD is implemented on a case-by-case basis through the discussion in a multi-disciplinary cancer board at each institution because the outcomes of each treatment for circumferential SESCCs remain unclear.²

Aims & Methods

This multicenter prospective observational study aimed to reveal the outcomes of each treatment for circumferential SESCCs. Patients with cT1a-EP/LPM or cT1a-MM/T1b-SM1 N0M0 SESCCs involving the entire circumference were enrolled in this study. At this stage, short-term outcomes, such as the proportion of curative resection after ESD, complete response (CR) after CRT/radiotherapy (RT), and adverse events including esophageal stricture, were evaluated. Curative resection in ESD was defined as pT1a without lymphovascular invasion (LVI). Esophageal stricture was defined as inability to pass the ordinary-sized endoscope thorough the treated site, and refractory stricture was defined as stricture requiring ≥ 6 endoscopic balloon dilation procedures.

Results

A total of 126 patients with circumferential SESCCs were enrolled from 16 Japanese tertiary institutions between May 2021 and November 2024. ESD was performed for 90 (71.4%) patients including 6 undergoing stepwise ESD, surgery for 18 (14.3%), CRT for 16 (12.7%), and RT alone for 2 (1.6%). Median longitudinal length of tumor was 55 (range: 30–140) mm in the ESD group, 80 (50–150) mm in the surgery group, and 70 (30–100) mm in the CRT/RT group. Tumor depth was diagnosed as cEP/LPM in 65.4% (55/84) of the ESD group, 38.9% (7/18) of the surgery group, and 50.0% (9/18) of the CRT/RT group, and the others were diagnosed as cMM/SM1. As stricture prevention method after ESD, local injection or filling of triamcinolone (TA) alone was used in 9 patients (10.7%), and both local injection of TA and oral steroid of prednisolone were used in 75 (89.3%). Among the 63 patients who did not receive additional treatment after ESD, the proportion of stricture and refractory stricture were 46.0% (29/63) and 27.0% (17/63), respectively. Curative resection after ESD was achieved in 58 patients (69.0%), including 46 (83.6%) with cEP/LPM and 12 (41.4%) with cMM/SM1. Of 26 patients with non-curative resection after ESD, 20 (76.9%) received additional treatment of either surgery, CRT, or RT, while the remaining 6 opted for follow-up. Of 18 patients in the surgery group, 7 with cEP/LPM and 4 with cMM/SM1 were diagnosed as pT1aN0 without LVI, while the remaining 7 with cMM/SM1 were diagnosed as pT1b, 3 of whom had lymph node metastasis. Anastomotic stricture was observed in 11.1% (2/18) of patients treated with surgery. Of 18 patients in the CRT/RT group, CR was confirmed in all patients without forming stricture.

Conclusion

Considering the high curative resection rate, ESD could be indicated for circumferential SESCCs diagnosed as cEP/LPM. In contrast, the careful consideration may be required in indicating ESD for circumferential SESCCs diagnosed as cMM/SM1 due to its low curative resection rate. Long-term outcome needs to be confirmed for further treatment comparisons.

References

1. Ishihara R, Arima M, Iizuka T, et al. Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer. Dig Endosc. 2020; 32: 452–93.
2. Kadota T, Ishihara R, Hatta W, et al. Multi-institutional questionnaire on treatment strategies for superficial entire circumferential esophageal squamous cell carcinoma. DEN Open. 2023; 3: e206.

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

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.

Introduction

Gastroparesis is a disorder characterized by delayed gastric emptying without mechanical obstruction, leading to symptoms such as nausea, vomiting, abdominal pain, and bloating. Cannabis and its active compounds are thought to interact with the gastrointestinal system through cannabinoid receptors, influencing motility, sensation, and inflammation. Nevertheless, data pertaining to the interactions between cannabis use, gastric motility and gastrointestinal (GI) symptoms is still scant¹.

Aims & Methods

The aim of the current study was to compare GI symptoms and gastric motility in a cohort of patients referred for gastric emptying breath test (GEBT). In this prospective study, all consecutive patients referred for motility testing in a tertiary hospital were recruited. Following obtaining written informed consent, questionnaires, including ROME, SCL-90-R and SF36 were filled out by the patients. Carbon-13 spirulina GEBT was done performed according to protocol, following consumption of a standardized meal. Patients with ongoing (regular or occasional) cannabis use were compared with non-cannabis users for all symptoms, quality of life and GEBT testing results. An additional healthy cohort of volunteers was recruited for validation of GEBT cut-off values and comparison to the symptomatic cohort.

Results

A total of 88 patients and 14 healthy volunteers were included in the current study. Among patients, 15 (17%) were identified as cannabis users, and these were compared with 73 non-users. Mean age and gender did not differ between users and non-users (52.4 vs 43.0, and 21% vs 33% males, respectively, p=NS). Gastric emptying breath test results did not significantly differ between groups, both in terms of mean values (t^1/2 127.2 vs 129.2 minutes, users versus non-users, respectively; p=NS) and in the proportion of delayed gastric emptying (26.7% versus 32.9%, users versus non-users, respectively; p=NS). None of the healthy volunteers displayed delayed gastric emptying results. Cannabis users demonstrated a higher gastrointestinal symptom burden and a greater number of diagnosed disorders of gut-brain interaction (DGBI) compared to non-users.

Conclusion

In our cohort of patients referred for gastric emptying breath tests, gastric emptying was similar between cannabis users and non-users. This is in line with previous studies suggesting that cannabis does not improve delayed gastric emptying. Nevertheless, previous studies suggested that cannabis may alleviate gastroparesis-associated symptoms². In this context, our results show that cannabis use was rather associated a more severe and systemic symptomatic manifestation of gut-brain disorders, in contrast to a more localized upper gastrointestinal involvement seen in non-users. Although causality cannot be established, we do note that despite ongoing cannabis use, treatment response was sub-optimal in the user patient group. Factors contributing to these differences, such as physiological or psychological constructs, should be further explored.

References

¹Parkman HP et al. Marijuana Use in Patients with Symptoms of Gastroparesis: Prevalence, Patient Characteristics, and Perceived Benefit. Dig Dis Sci. 2020
²Barbash, B et al. Cannabinoids Lead to Significant Improvement in Gastroparesis—Related Abdominal Pain: 1204. American Journal of Gastroenterology 2018.