Design and Modelling of Continuum Robot for Endoscopic Submucosal Dissection Surgery With Lifting Force Estimation.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for early-stage gastrointestinal cancers. However, traditional surgical instruments lack accuracy and force-sensing. METHODS: A new type of continuum robot for ESD is designed. An accurate static model of the proposed continuum robot is established, considering cases where the robot bends into C-shapes and S-shapes. A force estimation method based on an accurate static model is proposed. Then, the accuracy of the static model and force estimation is verified through experiments. Finally, an ex-organ experiment is carried out. RESULTS: The average position error of the proposed static model is 0.72 mm, accounting for 2.57% of the total robot length. The average error of force estimation is 19.53 mN. By gripping and cutting ex-porcine gastric mucosa, the robot's functionality is validated. CONCLUSION: This paper contributes to precise control and safe interaction of continuum robots.

Transparent Cap-Assisted Blunt Endoscopic Dissection of Gastric Submucosal Tumours Smaller than 2cm.

OBJECTIVE: To evaluate the safety and effectiveness of transparent cap-assisted blunt dissection (TCABD) in the endoscopic resection of gastric submucosal tumours (G-SMT) smaller than 2cm, as compared with conventional electronic knife dissection. STUDY DESIGN: Randomised controlled analysis. Place and Duration of the Study: Department of Gastrointestinal Surgery, The School of Clinical Medicine, Fujian Medical University, The First Hospital of Putian City, Putian, China, from July 2020 to 2022. METHODOLOGY: Fifty-eight patients having G-SMT smaller than 2cm were included. They were randomly divided into two groups; undergoing transparent cap-assisted blunt dissection (BD group) and conventional endoscopic submucosal excavation (ESE group). The pathology, lesion size in long diameter (mm), operation time, the number of clips used to close the wounds, the number of snare used to resect the tumour, hospital days, hospitalisation expense, en bloc resection rate, and the complications including perforation, postoperative bleeding, and postoperative infection were compared between the two groups. RESULTS: The mean long diameter in the BD group was 9.6 ± 3.6mm, while the conventional ESE group was 10.7 ± 4.5mm. As compared with the conventional ESE group, the operation time, the number of clips used to close the wounds, the number of snare used to resect the tumours, the hospital days, and the hospitalisation expense were all significantly decreased (p <0.05). The perforation rate was lower in the BD group (p <0.05). CONCLUSION: TCABD was effective and safe in the endoscopic resection of G-SMT smaller than 2cm. TCABD could help to reduce the perforation rate, shorten the operation time and hospital days, and decrease the hospitalisation expense in the endoscopic resection of G-SMT. KEY WORDS: Endoscopic submucosal excavation, Endoscopic full-thickness resection, Endoscopic resection, Submucosal tumour, Transparent cap-assisted blunt dissection.

Efficacy of a novel traction method: outside-lesion clip-thread method for gastric endoscopic submucosal dissection of lesions of the greater curvature of the upper/middle stomach (with video).

BACKGROUND: Gastric endoscopic submucosal dissection (ESD) for lesions located on the greater curvature of the upper and middle (U/M) third of the stomach remains challenging, even for experienced endoscopists. Accordingly, we have developed a novel traction technique, termed the outside-lesion clip-thread method (O-CTM). In this method, a clip thread is attached to the healthy mucosa outside the circumferential incision line, and traction is applied to bring the scope and lesion into proximity for ESD. Here, we assessed the efficacy of ESD using the O-CTM compared to ESD without the O-CTM. METHODS: We retrospectively reviewed data from 63 consecutive patients who underwent gastric ESD for 63 lesions located on the greater curvature of the U/M third of the stomach between September 2015 and April 2024. The primary outcome was the operation time, and secondary outcomes were resection speed, en bloc resection, R0 resection and complications in the O-CTM and without O-CTM ESD groups. RESULTS: Of the 63 included lesions, 37 were resected without the O-CTM between September 2015 and June 2022 (without O-CTM group), and 26 lesions were resected using the O-CTM between July 2022 and April 2024 (O-CTM group). The O-CTM group had significantly shorter operation times (40 min vs. 77 min, p = 0.01) than the without O-CTM group. The resection speed was also significantly faster (20.1 mm2/min vs. 11.3 mm2/min, p = 0.02). No significant differences in en bloc resection rate, R0 resection rate, and complications were observed. CONCLUSIONS: Gastric ESD using O-CTM is beneficial when compared with the ESD without O-CTM in reducing operation time and improving resection speeds for treating lesions located on the greater curvature of the U/M region.

Gastric cystica profunda: Another indication for minimally invasive endoscopic resection techniques?

Gastric cancer presents a significant global health burden, as it is the fifth most common malignancy and fourth leading cause of cancer mortality worldwide. Variations in incidence rates across regions underscores the multifactorial etiology of this disease. The overall 5-year survival rate remains low despite advances in its diagnosis and treatment. Although surgical gastrectomy was previously standard-of-care, endoscopic resection techniques, including endoscopic mucosal resection and endoscopic submucosal dissection (ESD) have emerged as effective alternatives for early lesions. Compared to surgical resection, endoscopic resection techniques have comparable 5-year survival rates, reduced treatment-related adverse events, shorter hospital stays and lower costs. ESD also enables en bloc resection, thus affording organ-sparing curative endoscopic resection for early cancers. In this editorial, we comment on the recent publication by Geng et al regarding gastric cystica profunda (GCP). GCP is a rare gastric pseudotumour with the potential for malignant progression. GCP presents a diagnostic challenge due to its nonspecific clinical manifestations and varied endoscopic appearance. There are several gaps in the literature regarding the diagnosis and management of GCP which warrants further research to standardize patient management. Advances in endoscopic resection techniques offer promising avenues for GCP and early gastric cancers.

Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer.

OBJECTIVES: We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: From EGC patients who underwent ESD, bulk RNA sequencing was performed on non-cancerous gastric mucosa samples at the time of initial EGC diagnosis. This included 23 patients who developed MGC, and 23 control patients without additional gastric neoplasms for over 3 years (1:1 matched by age, sex, and Helicobacter pylori infection state). Candidate differentially-expressed genes were identified, from which biomarkers were selected using real-time quantitative polymerase chain reaction and cell viability assays using gastric cell lines. An independent validation cohort of 55 MGC patients and 125 controls was used for marker validation. We also examined the severity of gastric intestinal metaplasia, a known premalignant condition, at initial diagnosis. RESULTS: From the discovery cohort, 86 candidate genes were identified of which KDF1 and CDK1 were selected as markers for MGC, which were confirmed in the validation cohort. CERB5 and AKT2 isoform were identified as markers related to intestinal metaplasia and were also highly expressed in MGC patients compared to controls (p < 0.01). Combining these markers with clinical data (age, sex, H. pylori and severity of intestinal metaplasia) yielded an area under the curve (AUC) of 0.91 (95% CI, 0.85-0.97) for MGC prediction. CONCLUSION: Assessing biomarkers in non-cancerous gastric mucosa may be a useful method for predicting MGC in EGC patients and identifying patients with a higher risk of developing MGC, who can benefit from rigorous surveillance.

Risk factors for pathological upgrading and noncurative resection in patients with gastric mucosal lesions after endoscopic submucosal dissection.

BACKGROUND: The pathological results obtained from endoscopic forceps biopsy (EFB) do not always align with the findings of postoperative endoscopic submucosal dissection (ESD). Furthermore, as ESD becomes more widespread, the number of noncurative endoscopic cases increases; thus, an accurate preoperative diagnosis and an appropriate treatment method are crucial. The purpose of this study was to explore the risk factors for postoperative pathological upgrading and noncurative resection and to gather experience in clinical and pathological diagnosis. METHODS: From March 2016 to November 2023, 292 ESD specimens were collected from 262 patients with gastric mucosal lesions. Clinicopathological information, the coincidence rate of pathological diagnosis between EFB and ESD specimens, and risk factors related to noncurative resection were analyzed retrospectively. RESULTS: The overall upgraded pathological diagnosis rate between EFB and ESD was 26.4%. The independent predictors for the upgraded group included proximal stomach lesions, lesion size > 2 cm, surface ulceration, and surface nodules. Twenty of the 235 early gastric cancer (EGC) patients underwent noncurative ESD resection. Multivariate analysis showed that undifferentiated carcinoma and tumor infiltration into the submucosa were significantly associated with noncurative resection. CONCLUSION: Biopsy cannot fully represent the lesions of gastric intraepithelial neoplasia (GIN). When a suspected epithelial dysplasia is suspected, a careful endoscopic examination should be conducted to evaluate the lesion site, size, and surface characteristics to ensure an accurate diagnosis. Noncurative endoscopic resection is associated with undifferentiated carcinoma and submucosal infiltration. Clinicians must be familiar with these predictive factors for noncurative resection and select the appropriate treatment for their patients.

The staining results of early gastric cancer by indigo carmine chromoendoscopy associated with histological structure: a retrospective study.

BACKGROUND: At present, conventional endoscopy and chromoendoscopy using indigo carmine (IC) is a very useful method to determine the demarcation line (DL) of early gastric cancer lesions, but it is not suitable for all lesions. AIMS: This study aimed to determine the applicable conditions for IC chromoendoscopy. METHODS: We retrospectively evaluated 187 lesions in 181 patients who had an endoscopic diagnosis of EGC and were treated with endoscopic submucosal dissection (ESD). According to the existence of the DL between the lesion mucosa and normal mucosa with IC chromoendoscopy, the lesions were divided into two groups: clear group and unclear group. Clinicopathological characteristics were evaluated in each group. From January 2022 to March 2023, the postoperative pathological sections of 19 lesions (81 slices) in the clear group and 19 lesions (80 slices) in unclear group were scanned with high definition, and the crypt structure between the two groups was evaluated. RESULTS: There was no significant difference in clinical factors between the clear group and unclear group. There were significant differences in crypt area, crypt length, and crypt opening diameter between the two groups. In the clear group, there were significant differences in crypt area, crypt length, and crypt opening diameter between the normal area and cancer area, but there was no significant difference in the unclear group. CONCLUSIONS: The margins of lesions with fused or absent crypt structures, a small crypt area, a short crypt length, and a short crypt opening diameter can be easily determined with IC chromoendoscopy.

Development and validation of a predictive model for submucosal fibrosis in patients with early gastric cancer undergoing endoscopic submucosal dissection: experience from a large tertiary center.

BACKGROUND: Submucosal fibrosis is associated with adverse events of endoscopic submucosal dissection (ESD). The present study mainly aimed to establish a predictive model for submucosal fibrosis in patients with early gastric cancer (EGC) undergoing ESD. METHODS: Eligible patients with EGC, identified at Qilu Hospital of Shandong University from April 2013 to December 2023, were retrospectively included and randomly split into a training set and a validation set in a 7:3 ratio. Logistic regression analyses were used to pinpoint the risk factors for submucosal fibrosis. A nomogram was developed and confirmed using receiver operating characteristic (ROC) curves, calibration plots, Hosmer-Lemeshow (H-L) tests, and decision curve analysis (DCA) curves. Besides, a predictive model for severe submucosal fibrosis was further conducted and tested. RESULTS: A total of 516 cases in the training group and 220 cases in the validation group were recruited. The nomogram for submucosal fibrosis contained the following items: tumour location (long axis), tumour location (short axis), ulceration, and biopsy pathology. ROC curves showed high efficiency with an area under the ROC of 0.819 in the training group, and 0.812 in the validation group. Calibration curves and H-L tests indicated good consistency. DCA proved the nomogram to be clinically beneficial. Furthermore, the four items were also applicable for a nomogram predicting severe fibrosis, and the model performed well. CONCLUSION: The predictive models, initially constructed in this study, were validated as convenient and feasible for endoscopists to predict submucosal fibrosis and severe fibrosis in patients with EGC undergoing ESD.

Optimal Surveillance of Metachronous Gastric Lesion after Endoscopic Resection of Early Gastric Cancer.

Endoscopic resection (ER)-a minimal invasive procedure, compared to surgical gastrectomy, with the advantage of preserving the entire stomach and maintaining the patient's quality of life-is a widely used curative treatment for early gastric cancers (EGCs). Despite its advantages, such as the preservation of the whole stomach, a large area of the gastric mucosa with histologic changes such as atrophy and intestinal metaplasia remains after ER, and so does the risk of metachronous gastric cancers (MGCs). Therefore, regular surveillance endoscopy after curative ER of EGCs is important so that MGCs are detected early and so minimally invasive ER remains a treatment option. To date, the optimal interval for surveillance endoscopy after curative ER of EGCs has not been established. Therefore, this review summarizes the results of the published studies on this topic with the aim of establishing the optimal surveillance interval for early identification of MGCs. Based on my review, the median timing of MGC occurrence is within 3 years, and reports suggest biannual endoscopy during the first 3 years; however, the evidence suggests that individual patient characteristics may influence the risk of MGCs. Therefore, stratified endoscopic strategies for surveillance based on patient characteristics, such as age, family history of gastric cancer, synchronous gastric lesions, and corpus intestinal metaplasia, should be applied.

Local recurrence after endoscopic submucosal dissection of gastric neoplastic lesions: special attention should be given also to safety margins.

INTRODUCTION: The incidence of local recurrence following gastric endoscopic submucosal dissection (ESD) remains a clinical concern. We aimed to evaluate the impact of narrow safety margin (< 1 mm) on the recurrence rate. METHODS: A retrospective cohort study was conducted across two centers. Cases of R0-ESD with subsequent recurrence were compared to matched controls in a 1:2 ratio in a case-cohort analysis. RESULTS: Over a median period of 25 months (IQR 14-43), a recurrence rate of 3% (95%CI 1.7-4.3) was observed, predominantly (13/21) following R0 resections with favourable histology. Endoscopic retreatment was feasible in 18 of 21 recurrences. The proportion of R0-cases where the safety margin in both horizontal (HM) and vertical (VM) margin exceeded 1 mm was similarly distributed in the recurrence and non-recurrence group, representing nearly 20% of cases. However, cases with HM less than 1 mm, despite VM greater than 1 mm, nearly doubled in the recurrence group (7.7% vs. 3.9%), and tripled when both margins were under 1 mm (23.1% vs. 7.7%). Despite this trend, statistical significance was not achieved (p = 0.05). In the overall cohort, the only independent risk factor significantly associated with local recurrence was the presence of residual tumor at the HM (HM1) or not assessable HM (HMx) (OR 16.5 (95%CI 4.4-61.7), and OR 11.7 (95%CI 1.1-124.1), respectively). CONCLUSIONS: While not common or typically challenging to manage, recurrence post-ESD warrants attention and justifies rigorous post-procedural surveillance, especially in patients with HM1, HMx, and probably also in those with R0 resections but narrow safety margin.

Gastric microbiome signature for predicting metachronous recurrence after endoscopic resection of gastric neoplasm.

BACKGROUND: Changes in gastric microbiome are associated with gastric carcinogenesis. Studies on the association between gastric mucosa-associated gastric microbiome (MAM) and metachronous gastric cancer are limited. This study aimed to identify gastric MAM as a predictive factor for metachronous recurrence following endoscopic resection of gastric neoplasms. METHOD: Microbiome analyses were conducted for 81 patients in a prospective cohort to investigate surrogate markers to predict metachronous recurrence. Gastric MAM in non-cancerous corporal biopsy specimens was evaluated using Illumina MiSeq platform targeting 16S ribosomal DNA. RESULTS: Over a median follow-up duration of 53.8 months, 16 metachronous gastric neoplasms developed. Baseline gastric MAM varied with Helicobacter pylori infection status, but was unaffected by initial pathologic diagnosis, presence of atrophic gastritis, intestinal metaplasia, or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence but showed significant difference in ß-diversity. The study population could be classified into two distinct gastrotypes based on baseline gastric MAM: gastrotype 1, Helicobacter-abundant; gastrotype 2: Akkermansia-abundant. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype (Cox proportional hazard analysis, adjusted hazard ratio [95% confidence interval]: 5.10 [1.09-23.79]). CONCLUSIONS: Gastric cancer patients can be classified into two distinct gastrotype groups by their MAM profiles, which were associated with different risk of metachronous recurrence.

Unveiling clinicopathologic features and outcomes for endoscopic submucosal dissection of early gastric cancer at gastric angulus in China.

BACKGROUND: With advances in endoscopic submucosal dissection (ESD) technique, an increasing number of the Chinese population are being diagnosed with early gastric cancers (EGCs) at gastric angulus. However, the relationship between gastric angulus and EGCs remains obscure. OBJECTIVES: We aimed to unveil the unreported location characteristics of gastric angulus in Chinese EGC patients and the correlation between the degree of submucosal fibrosis and ESD outcomes. METHODS: We retrospectively reviewed the medical records of EGC patients treated with ESD from January 2010 to March 2023. We retrospectively investigated and analyzed 740 EGC patients using multiple analyses. RESULTS: Following gastric antrum (53.1%), the gastric angulus (21.8%) emerged as the second-most prevalent site for EGCs. It had highest incidence of severe submucosal fibrosis and ulceration than the other parts. Multivariate analysis showed independent associations of submucosal fibrosis at the angulus with ulceration (OR: 3.714, 95% CI: 1.041-13.249), procedure duration (OR: 1.037, 95% CI: 1.014-1.061), and perforation complication (OR: 14.611, 95% CI: 1.626-131.277) (all P < 0.05). CONCLUSIONS: The gastric angulus demonstrates the highest incidence of severe submucosal fibrosis and ulceration for EGCs identified by ESD. This condition is linked to unfavorable outcomes, typically increased perforation risks and prolonged operation duration. Therefore, meticulous dissection is crucial for patients with EGCs in the gastric angulus.

Efficacy of robot arm-assisted endoscopic submucosal dissection in live porcine stomach (with video).

Endoscopic submucosal dissection (ESD) is technically challenging and requires a high level of skill. However, there is no effective method of exposing the submucosal plane during dissection. In this study, the efficacy of robot arm-assisted tissue traction for gastric ESD was evaluated using an in vivo porcine model. The stomach of each pig was divided into eight locations. In the conventional ESD (C-ESD) group, one ESD was performed at each location (N = 8). In the robot arm-assisted ESD (R-ESD) group, two ESDs were performed at each location (N = 16). The primary endpoint was the submucosal dissection speed (mm2/s). The robot arm could apply tissue traction in the desired direction and successfully expose the submucosal plane during submucosal dissection in all lesion locations. The submucosal dissection speed was significantly faster in the R-ESD group than in the C-ESD group (p = 0.005). The blind dissection rate was significantly lower in the R-ESD group (P = 0.000). The robotic arm-assisted traction in ESD enabled a significant improvement in submucosal dissection speed, blind dissection rate which suggests the potential for making ESD easier and enhancing procedural efficiency and safety.

Clinicopathological Characteristics and Lymph Node Metastasis Rates in Early Gastric Lymphoepithelioma-Like Carcinoma: Implications for Endoscopic Resection.

Background/Aims: Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of gastric cancer. We aimed to identify the clinicopathological features and rate of lymph node metastasis (LNM) to investigate the feasibility of endoscopic submucosal dissection for early gastric LELC confined to the mucosa or submucosa. Methods: We compared the clinicopathological characteristics of 116 early gastric LELC patients and 5,753 early gastric well- or moderately differentiated (WD or MD) tubular adenocarcinoma patients treated by gastrectomy. Results: Compared to WD or MD early gastric cancer (EGC) patients, early LELC patients were younger and had a higher prevalence of proximally located tumors. Despite more frequent deep submucosal invasion (86.2% vs 29.8%), lymphatic invasion was less frequent (6.0% vs 16.2%) in early LELC patients than in WD or MD EGC patients. Among tumors with deep submucosal invasion, the tumor size was smaller, lymphatic invasion was less frequent (6.0% vs 40.2%) and the rate of LNM was lower (10.0% vs 19.4%) in patients with LELC than in those with WD or MD EGC. The overall rate of LNM in early LELC patients was 8.6% (10/116). The risk of LNM in patients with mucosal, shallow submucosal invasive, or deep submucosal invasive LELC was 0% (0/6), 0% (0/10), and 10% (10/100), respectively. Conclusions: Early LELC is a distinct subtype of EGC with more frequent deep submucosal invasion but less lymphatic invasion and LNM than WD or MD EGCs. Endoscopic submucosal dissection may be considered curative for patients with early LELC confined to the mucosa or shallow submucosa, given its negligible rate of LNM.