Clinical Case Summary

A female patient, 67 years old, with no previous medical history, was referred to our hospital because of a metastatic sigmoid colon cancer (T3,Ν1c,M1a) that was found during colonoscopy for bright red blood per rectum and changes in bowel habits. The tumor occupied 80% of the lumen and following MDT discussion a laparoscopic anterior resection was performed. Patient recovered well and 3 weeks later recieved 6 cycles of FOLFOX.
Patient presented 1 month after the operation at the emergency department with abdominal distension, vomiting and inhibition of gas and fecal excretion.
Fluoroscopy and CT scan confirmed the anastomotic stenosis.
A flexible sigmoidoscopy was also performed in order to exclude local recurrence. An anastomotic stricture was recognized 8cm from the anal verge, preventing the passage of the diagnostic gastroscope 9,2mm.
EUS was also performed, which revealed 1cm hypoechoic stenosis and FNB biopsies were obtained, which showed inflammation and fibrosis, but no sign of local recurrence.
The patient underwent two flexible sigmoidoscopies with CRE balloon dilation up to 15mm, with no clinical or endoscopic response. It was then decided to proceed to LAMS placement under direct vision. A guide wire was passed through the stenosis using a dilatation balloon catheter under fluoroscopic guidance and then 20mm x10mm LAMS was successfully deployed at the anastomotic stricture. Dilation of the LAMS was performed with a CRE balloon at 12mm.
Then laparotomy and resection of 3 liver metastases was performed.
Eight weeks later a control flexible sigmoidoscopy was performed that showed the stent in good position with maintained patency. The stent was then removed with a rat-tooth forceps, with clean base ulcerations. Additional biopsies were obtained precautionally that were negative for malignancy.
Patient carried on with chemo while remaining asymptomatic for 6 months of follow-up period without any hospitalization for obstructive symptoms.

References

Baron T., Grimm I., and Irani S., Lumen-apposing covered self-expandable metal stents for short-length gastrointestinal strictures: will they take hold?, Endoscopy. (2017)
Santos-Fernandez J., Paiji C., Shakhatreh M. et al., Lumen-apposing metal stents for benign gastrointestinal tract strictures: an international multicenter experience, World Journal of Gastrointestinal Endoscopy. (2017)
Michael Coles, Pearl Uy, Victoria Madray, John Erikson Yap, Subbaramiah Sridhar, The Off-Label Use of a Lumen-Apposing Metal Stent (LAMS) for a Benign Colon Anastomotic Stricture Causing Recurrent Bowel Obstruction in a Patient with Keloids, Gastrointestinal Medicine. (2021)

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.

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.

Clinical Case Summary

A 75-year-old male under follow-up for chronic anemia secondary to multiple gastrointestinal angiodysplasias. He required transfusions every two weeks and maintained a baseline hemoglobin level of around 7–8 g/dL despite repeated therapeutic endoscopy with argon plasma coagulation. In light of this, he began daily treatment with oral Thalidomide 50 mg, with a good response for three years. At that point, he developed persistent melena and also experienced a deep vein thrombosis attributed to the treatment, leading to its discontinuation. The regimen was then changed to subcutaneous Octreotide 10 mg monthly, later intensified to 30 mg per month. Despite this, he continued to have recurrent gastrointestinal bleeding and multiple hospital admissions due to anemia-related symptoms. With no other treatment options available, a weekly dose of 30 mg was prescribed, achieving a good response for two years. Eventually, due to loss of efficacy and refractoriness to other treatments, compassionate use of Bevacizumab was initiated at a dose of 7.5 mg/kg monthly. From the beginning and after three doses, the patient became asymptomatic and experienced no further bleeding episodes, maintaining hemoglobin levels around 12–13 g/dL.
Gastrointestinal angiodysplasias are a common and significant condition due to the increased demand they place on healthcare services. Their management is complex, and treatment options are limited, particularly in cases that are refractory to standardized therapies. In such patients, the use of Bevacizumab can be considered. Although evidence is limited, it shows promising results, as demonstrated in our case.

References

Figure 1. Enteroscopy image showing angiodysplasia in the small intestine
Figure 2. Therapeutic enteroscopy, image prior to argon plasma coagulation therapy
Figure 3. Capsule endoscopy image showing angiodysplasia in the small intestine
Figure 4. Another capsule endoscopy image showing active bleeding secondary to one of the angiodysplasias

Introduction

Besides analgesia, opioids affect gastrointestinal (GI) motility, including decreased bowel peristalsis and delayed gastric emptying. Peripherally acting mu-opioid receptor antagonists, like naloxegol, are approved for treating opioid-induced constipation.

Aims & Methods

We aimed to evaluate the effects of naloxegol on opioid-induced lower GI tract dysfunction using magnetic resonance imaging (MRI) to assess changes in colonic volumes in healthy volunteers (HV).
In this double-blind, randomised, three-way crossover study, 15 HV complete three study visits, separated by ≥1 week washout, with administration of 25 mg naloxegol + 60 mg codeine, 60 mg codeine + placebo, or double placebo. During each visit, five abdominal MRI scans (each 20 min.) are obtained at 30 min intervals, at baseline, after drug intake, after a standardized 44 g oatmeal and 100 mL Nutridrink (313 kCal) meal, after a second drug dose, and after a bisacodyl 10 mg suppository administration. Colonic segmental volumes were quantified from all MRI scans using Entrolytics (Motilent, London, UK) in the ascending, transverse, descending, and rectosigmoid colon. We recorded the passage of stool during the study visit. Results are presented as medians with min. and max. P-values <0.05 are considered statistically significant. Adjusted p-values are used in case of post-hoc analysis.

Results

Interim analysis on 8 HVs (mean age 36±5y, 75% females) revealed that two subjects made stool on 2 mornings before the study visit. Four subjects passed stool in the double placebo group (2 postprandial, 2 post-bisacodyl), and 2 of them passed stool in the other 2 groups as well, around the same time. A significant scan x group effect was found for the whole colon volumes (p<0.05). More specifically, there was a significant difference in median ascending colon volumes between the scans (p=0.03), and especially in the double placebo group (Table). Although there was no significant difference in the median transverse colon volumes, bisacodyl led to a significant decrease in descending colon volume (p<0.0001), more specifically in the naloxegol+codein group and the double placebo group (ps<0.05), but not in the codein+placebo group. No significant differences in volumes of the rectosigmoid were detected.

Conclusion

Interim MRI analysis of 8 HVs suggests different colonic motility responses across groups and timepoints. Toilet visits were suppressed in both codeine groups. Different responses to drug and food intake were found in the ascending and descending colon between the naloxegol+codein and double placebo group on one hand compared to the codein+placebo group. Expansion and analysis of the full number of subjects will further clarify insights into the acute colonic responses to opioids and potential reversal by naloxegol.