Introduction

Currently, the Japanese guidelines for GISTs suggest endoscopic ultrasound-guided fine-needle aspiration for sampling the tissue of subepithelial tumors (SETs) and as a first-line technique. Mucosal incision-assisted biopsy (MIAB) is another tissue sampling technique; in this technique, the mucous membrane covering the SET is cut to expose and sample the tissue directly under direct visualization. However, the Japanese guidelines do not clearly state how to handle this technique, and the MIAB procedure has not been standardized, especially in technical aspects, the need for local injection to the submucosa before mucosal incision to prevent perforation, and the need for acid secretion inhibitors to prevent postoperative bleeding.

Aims & Methods

This systematic review and meta-analysis aimed to evaluate diagnostic ability and examine the efficacy of countermeasures to adverse events of MIAB for gastric SETs. We performed a literature search and identified 533 relevant articles. Eleven articles, including 339 lesions, were ultimately used in the meta-analysis. The primary endpoint was the pathological diagnostic rate of MIAB for gastric SETs, and the secondary endpoint was the incidence of adverse events. The efficacy of acid secretion inhibitors in preventing postoperative bleeding and that of local injection before incision to prevent perforation were also examined.

Results

Nine studies were performed in Japan and two in South Korea, of which only two were prospective studies. The mean age of the patients was 60.7 years, and 48.4% were male. In all studies, endoscopic ultrasound was performed to assess tumors before incision-assisted biopsy. The mucosal incision procedure was the same in all studies: The mucosal incision on the tumor was made, and tissue was sampled directly from the tumor using biopsy forceps; however, in all cases in eight articles and six cases in one article, a local injection of saline or glycerol into the submucosa before the mucosal incision was performed. Nine articles reported the closure of the incision using clips. The mean tumor diameter was 20.6 mm, and the pathological results included 150 GISTs, 70 leiomyomas, 11 schwannomas, 37 ectopic pancreas, three lipomas, three cases of inflammatory fibrotic polyp, two malignant lymphoma lesions, two glomus tumors, one neuroendocrine tumor, one adenocarcinoma, one old hematoma, and one renal cell carcinoma. In all cases in six articles and some in two, an intravenous or oral gastric acid suppressant such as esomeprazole or vonoprazan was administered after treatment. The pooled pathological diagnostic rate of MIAB for gastric SETs was 86.0% (95% confidence interval [CI]: 78.6–93.4; I² = 96%). The adverse event rate of the pooled population was 0.3% (95% CI: −1.15 – 1.76; I² = 0%). The acid secretion inhibitors significantly reduced postoperative bleeding (odds ratio: 0.06, 95% CI: 0.01– 0.66, P = 0.02). Perforation occurred in 0% and 2.6% of the local injection and non-local injection cohorts, respectively, and the pathological diagnostic rates were 50% and 66.7%, respectively.

Conclusion

MIAB is a reliable technique with a favorable diagnostic rate and few adverse events. Acid secretion inhibitors effectively prevent postoperative bleeding, but the effectiveness of local injection remains unclear. This technique is considered a robust tissue sampling method for gastric SETs.

References

None

Introduction

The Ki-67 labeling index is a well-established marker of cellular proliferation and has been associated with worse disease-free and overall survival in gastrointestinal stromal tumors (GISTs). Recent evidence highlights its potential role in risk stratification, particularly when Ki-67 exceeds certain thresholds. However, current assessment relies on postoperative histopathology. Radiomics, by extracting quantitative features from computer tomography (CT) images, may offer a non-invasive method to predict Ki-67 expression preoperatively. This meta-analysis aimed to evaluate the diagnostic performance of CT-based radiomics for predicting Ki-67 status in GISTs.

Aims & Methods

A systematic review and meta-analysis were conducted according to PRISMA guidelines). Four electronic databases (PubMed, Scopus, Science Direct, Cochrane Library) were searched for relevant articles up to December 2024. Eligible studies assessed CT radiomics in predicting Ki-67 in histologically confirmed GISTs. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated using a random-effects model. Subgroup analyses were performed based on cohort type, CT protocol, number of features, and Ki-67 cutoff values. Study quality was assessed using the QUADAS-2 tool.

Results

Six studies comprising 1,632 patients met the inclusion criteria. Pooled sensitivity and specificity were 0.71 (95% CI: 0.63–0.79) and 0.76 (95% CI: 0.73–0.78), respectively. The pooled AUC was 0.79 (95% CI: 0.74–0.84). Subgroup analyses showed consistent performance across imaging protocols and feature counts, while Ki-67 cutoffs (8% vs. 10%) significantly impacted diagnostic accuracy. Sensitivity analysis confirmed robustness of specificity estimates. Publication bias was detected for specificity (Egger’s test p = 0.006).

Conclusion

CT radiomics demonstrates moderate accuracy for non-invasively predicting Ki-67 expression in GISTs. Given Ki-67's prognostic significance, radiomics could support preoperative risk assessment and personalized treatment planning. Further prospective validation is warranted.

Disclosure

No Conflict of Interest ​

Introduction

​Endocytoscopy (ECS), an ultrahigh-magnification contact-type endoscopy, enables real-time visualization of gastrointestinal mucosal and neoplastic cells. As a result, ECS enhance diagnostic precision as a form of optical biopsy. However, the reliability of ECS diagnosis is contingent upon adequate staining, which remains a considerable challenge in the stomach due to the abundance of mucus and inflammatory exudates that hinder optimal visualization. Weak vital staining can easily reduce the reliability of ECS diagnosis. Texture and Color Enhancement Imaging (TXI), a digital image enhancement modality developed by Olympus, enhances three key imaging elements—brightness, texture, and color tone—to optimize lesion visualization even under suboptimal staining conditions. Consequently, TXI may augment the diagnostic utility of ECS.

Aims & Methods

The aim of this study was to evaluate whether TXI enhances the diagnostic performance of ECS in early gastric cancer. Twenty-eight patients with 30 gastric cancers scheduled for magnifying endoscopic examination at Nippon Medical School Tama Nagayama Hospital between February 2024 and March 2025 were prospectively enrolled. All ECS procedures were performed with GIF-H290EC (Olympus Co., Tokyo, Japan) and the video processors EVIS X1 (Olympus Co., Tokyo, Japan). For in vivo dyeing, double staining with crystal violet and methylene blue was used. ECS was performed with and without TXI in both cancer and non-cancerous legions. ECS observation is performed by first taking photographs without TXI, and then taking photographs of the same area using the TXI. From each lesion, five ECS images with and without TXI were selected, resulting in a blinded and randomized image catalog (comprising 300 images from 30 gastric cancers and 280 images from 28 non-tumor areas). Two endoscopists independently assessed the images using a numerical rating scale (NRS, 0–10) to evaluate the visibility of nuclear atypia and structural cellular atypia. Diagnostic accuracy was assessed against pathological diagnosis as the gold standard. ECS diagnoses were rendered based on previously established criteria, wherein lesions exhibiting high-grade atypia were classified as cancer (Kaise M, et al. Endoscopy. 2015).

Results

The overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for EGC diagnosis by the two endoscopists were 82.5%, 84.3%, 80.7%, 81.3%, and 83.8%, respectively. The rate of interobserver agreement between the two endoscopists was high, with a kappa coefficient of κ = 0.797. Notably, diagnostic accuracy was significantly higher in the TXI images compared to the non-TXI images (85.2% vs. 79.0%, p = 0.0027). While the NRS scores for structural atypia did not differ significantly between the TXI and non-TXI images (4.90 vs. 4.87, p = 0.61), the NRS scores for nuclear atypia were significantly elevated in the TXI images (6.88 vs. 5.88, p < 0.0001).

Conclusion

​The integration of TXI with ECS significantly enhances the visualization of nuclear atypia and improves diagnostic accuracy in the diagnosis of gastric cancer. This synergistic approach facilitates superior optical biopsy capabilities, enhancing its clinical utility in the endoscopic diagnosis of early gastric cancer.

References

Kaise M, Ohkura Y, Iizuka T, Kimura R, Nomura K, Kuribayashi Y, et al. Endocytoscopy is a promising modality with high diagnostic accuracy for gastric cancer. Endoscopy. 2015;47:19–25.

Introduction

Endoscopic treatment using peroral/anal flexible endoscopy and dedicated through-the-scope electrocautery devices has been developed as a less-invasive intraluminal surgery. However, pure endoscopic treatment has limitations for lesions at the deeper layer or excessively close to the mouth/anus. Conversely, surgical approach sometimes leads to wider resection and subsequent decreases in the patient’s quality of life. Collaborative surgery by both endoscopists and surgeons is considered effective for providing less-invasive local resection of gastrointestinal tumours to offset limitations either in pure endoscopic treatments or surgical intervention.

Aims & Methods

To investigate the feasibility and safety of this approach, we here retrospectively evaluated the clinical outcomes of collaborative surgery with endoscopists and surgeons. We consecutively collected data of patients who underwent collaborative surgery for lesions located from the laryngopharynx to the anus between October 2017 and December 2023. Collaborative surgery was indicated after the agreement on both flexible endoscopists and surgeons, considering possible benefits of the cooperation in terms of invasiveness, technical difficulty, and safety. Laryngopharyngeal lesions and cervical oesophageal cancer were removed using the ESD technique under laryngeal expansion using a curved laryngoscope by the otolaryngologist’s manipulation. With gastrointestinal surgeons, subepithelial tumours in the gastrointestinal tract and deeply invasive gastric cancers were removed in a full-layered fashion, followed by surgical suturing. Large duodenal cancers were principally treated by ESD followed by sero-muscular suturing for the reinforcement of the mucosal defects. In large anal canal cancer with pagetoid spread, a dermatologist externally dissected the perianally expanded area following ESD from the rectal side. Collaboration completeness, technical success, procedure time, postoperative hospitalization period, and occurrence of adverse events were analyzed.

Results

Collaboration surgery was performed for 134 lesions (33 laryngopharyngeal, 2 oesophageal, 89 gastric, 8 duodenal, and 2 recto-anal lesions, respectively) in 131 patients. Collaboration completeness was achieved in 129 lesions (96%). The en-bloc resection and pathological R0 resection of lesions were obtained in 127 (95%) and 124 (93%) lesions, respectively. The mean procedure time was 188 min. Patients were discharged on the mean postoperative day of 11. Five patients (4%) developed relevant postoperative adverse events.

Conclusion

The results indicated that collaborative surgery by endoscopists and surgeons was feasible and safe, and should contribute to providing less-invasive treatment than conventional approaches. The frequency of adverse events was considered acceptable. Collaborative surgery is worth considering as a flexible and reliable surgical option when cooperation should outperform a single treatment by either of endoscopists or surgeons. To establish this concept, further accumulation of cases and pieces of evidence by well-designed studies is desired.

Introduction

Esophageal Squamous Cell Carcinoma (ESCC) remains a significant global health problem with few therapeutic options and poor prognosis. Camrelizumab, an anti-PD-1 immune checkpoint inhibitor, has been shown in clinical trials to be of potential value in the treatment of advanced or metastatic ESCC as monotherapy or in combination with chemotherapy or anti-angiogenic therapy.

Aims & Methods

The aim of this study is to evaluate the clinical efficacy and safety profile of Camrelizumab in patients with esophageal squamous cell carcinoma, with the main outcomes being progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events.
We conducted a comprehensive search of PubMed, Scopus, Web of Science, Embase, and Cochrane from their inception to April 2025, focusing on randomized controlled trials (RCTs) and observational studies evaluating Camrelizumab for the treatment of esophageal squamous cell carcinoma. Meta-analyses utilized a random-effects model to calculate odds ratios, mean differences, and 95% confidence intervals for adverse events and total patients.

Results

Out of 1,563 studies initially screened, 15 studies met the inclusion criteria for our meta-analysis, comprising adult patients. Meta-analysis established a median progression-free survival (PFS) of 7.60 months (95% CI: 6.00–9.19). The major pathological response rate (MPR) was 0.42 (95% CI: 0.37–0.48), and the objective response rate (ORR) was 0.53 (95% CI: 0.38–0.68). The R0 resection rate was also remarkably high at 0.98 (95% CI: 0.96–1), and the disease control rate (DCR) was 0.87 (95% CI: 0.64–1). The pathological complete response rate (pCR) was 0.31 (95% CI: 0.20–0.43).
Regarding safety, the most common treatment-related adverse events were leukopenia 0.45 (95% CI: 0.23–0.68), neutropenia 0.30 (95% CI: 0.19–0.41), anemia 0.14 (95% CI: 0.03–0.29), thrombocytopenia 0.09 (95% CI: 0.03–0.17), and elevated transaminases 0.06 (95% CI: 0.02–0.12). Pneumonia 0.17 (95% CI: 0.11-0.23) and hypertension 0.12 (95% CI: 0.06-0.19) were the other immune-related adverse events. The majority of these events were tolerable and within safe parameters.

Conclusion

Camrelizumab demonstrates promising efficacy in the treatment of esophageal squamous cell carcinoma with satisfactory rates of ORR, MPR, and R0 resection. The safety profile is acceptable with controllable adverse effects. These findings support the potential therapeutic value of camrelizumab as a significant treatment strategy in multimodal treatment of esophageal squamous cell carcinoma and the need for further research to optimize its clinical use.

Introduction

We have focused on the morphology of subepithelial tumors (SETs) and examined the possibility of noninvasive differentiation method based on differences in tumor morphology on endoscopic ultrasonography (EUS) still images. In a previous study, we found that leiomyoma has a lower circularity (4π×area/perimeter²; range = 0-1, 1 = a true circle) on EUS images than gastrointestinal stromal tumor (GIST) and schwannoma in lesions ≥2 cm, and that two-dimensional morphological evaluation was useful for the differentiation of gastrointestinal mesenchymal tumors (GIMTs) (Koizumi E, et al. Digestion 2022). In this study, we performed an interim analysis of the prospective study to assess the validity of this concept including lesions ≥1 cm, and further examined the feasibility of three-dimensional evaluation by measuring sphericity (a surface area of a sphere having the same volume as the object divided by a surface area of the object; range = 0-1, 1 = a true sphere) by using CT images.

Aims & Methods

For 54 cases of 1-5 cm gastric GIMTs with pathological diagnosis accumulated at two institutions from 2020 to the present, one representative EUS image, which showed a maximum cross-sectional surface of tumors, was selected. Two endoscopists who were blind to the histology of lesions independently measured the circularity three times per image by using an image analyzing software, and an average of six values in total was defined as individual circularity of each lesion for the analysis. Then, circularity of the leiomyoma group and the GIST + schwannoma group were compared, and the diagnostic performance at the optimal cutoff value was evaluated. Additionally, in four GIMT cases that had undergone thin-slice CT before the tissue sampling, we attempted to construct the lesion in three-dimensional image and measure the sphericity.

Results

The number of cases of leiomyoma/GIST/schwannoma were 8/42/4, respectively, and the mean tumor diameter was 14/22/25 mm, respectively. The circularity of the leiomyoma group was significantly lower than that of the GIST+ schwannoma group (0.83 vs. 0.90, p = 0.005), with a cutoff value of 0.92 and the highest diagnostic rate of 63% (area under the curve = 0.80, sensitivity 57%, specificity 100%). In addition, sphericity could be measured in all four cases in which three-dimensional evaluation was performed (one leiomyoma case and three GIST cases), and the mean value of calculated sphericity was 0.84.

Conclusion

The interim analysis suggested that two-dimensional morphological evaluation of SETs would be useful for differentiating leiomyoma even in small lesions by using the circularity assessment. It was also possible to construct a three-dimensional structure, which could more adequately represent the overall shape and expected more precise morphological evaluation by using the sphericity evaluation.

Introduction

Barrett’s esophagus (BE) is known to be a precursor of esophageal and gastroesophageal junctional adenocarcinoma¹. Adenocarcinoma of the esophagus based on BE is still relatively rare in Japan, but the Westernization of dietary habits, the increase in obese patients, and the eradication of Helicobacter pylori (HP) infection may increase the number of cases in the future. In Japan, the prevalence of long-segmented BE (LSBE), which is common in the Western world, is relatively low, whereas SSBE is frequently observed². Atrophic gastritis (AG) caused by HP infection is also frequently observed in Japan, and the diagnosis of Japanese SSBE may be modulated by HPinfection/AG. In this study, we retrospectively investigated whether the morphology of SSBE could be influenced by HP status.

Aims & Methods

In our institution, 60 patients who had endoscopic ultra-short segmented Barrett’s esophagus (USBE; length of <1cm) were retrospectively collected and divided into two groups: 30 cases with AG caused by current HP infection (AG group) or without AG (non-AG group). As patient characteristics, we investigated age, sex, presence of reflux esophagitis (RE), presence of hiatus hernia, and use of proton pump inhibitor (PPI) therapy from the medical records. To objectively evaluate the roughness of the SCJ, we compared the morphology of USBE by measuring the respective perimeters of EGJ and SCJ, followed by the calculation of the SCJ/EGJ ratio. As a sub-analysis in the AG group, the SCJ/EGJ ratio was similarly compared in terms of the degree of AG (closed-type, n = 3; open-type, n = 27) according to the Kimura-Takemoto classification.

Results

In terms of patient characteristics, the median age was higher in the AG group than in the non-AG group (72 years old vs. 49 years old, p <0.001), and RE was less common in the AG group than in the non-AG group (3% vs. 36%, p = 0.004). There were no statistical differences between the two groups in sex, presence of hiatus hernia, and use of PPI. The mean SCJ/EGJ ratio was significantly higher in the AG group than in the non-AG group (2.26 vs. 1.43, p <0.001). In the sub-analysis, the mean SCJ/EGJ ratio was likely to be higher in open-type atrophy than in closed-type atrophy (2.33 vs. 1.58, p = 0.092).

Conclusion

In endoscopically diagnosed USBE, the circumference of SCJ appeared rough in the AG group, which suggested that the morphology of BE is influenced by HP infection and subsequent AG development. Particularly in Japan, simple rough margins of SCJ influenced by HP/AG may be estimated as USBE. In diagnosing BE, the morphological characteristics of SCJ and the HP/AG status should be taken into consideration.

References

1. Haggitt RC et al. Barrett's esophagus, dysplasia, and adenocarcinoma. Hum Pathol. 1994; 25: 982-93.
2. Manabe N et al. Does short-segment columnar-lined esophagus elongate during a mean follow-up period of 5.7 years? Dig Endosc. 2011; 23: 166-72.

Disclosure

There is no conflict of interest in this study.