Innovative submucosal injection solution for endoscopic resection with phosphorylated pullulan: a preclinical study.

BACKGROUND AND AIMS: A submucosal injection solution is used to assist in endoscopic surgery. The high viscosity of current solutions makes them difficult to inject. In the present study, we developed an extremely low-viscosity, easy-to-use submucosal injection solution using phosphorylated pullulan (PPL). METHODS: The PPL solutions were prepared at different concentrations, and their viscosities were measured. The mucosal elevation capacity was evaluated using excised porcine stomachs. Controls included 0.4% sodium hyaluronate (SH), 0.6% sodium alginate (SA), and saline. To evaluate the practicality, the catheter injectability of 0.7% PPL was measured, and EMR and endoscopic submucosal dissection (ESD) were performed using the stomach and colorectum of live pigs. As controls, 0.4% SH and saline were used. RESULTS: The PPL solutions were of extremely low viscosity compared to the solutions of 0.4% SH and 0.6% SA. Nevertheless, the mucosal elevation capacity of PPL solutions for up to 0.7% concentration was similar to that of 0.4% SH, and 0.7% PPL was less resistant to catheter infusion than 0.4% SH and 0.6% SA. In live pig experiments with endoscopic mucosal resection and ESD, snaring after submucosal injection of 0.7% PPL was easier than with 0.4% SH, ESD with 0.7% PPL produced less bubble formation than with 0.4% SH, and the procedure time tended to be shorter with 0.7% PPL than with 0.4% SH because of the shorter injection time. CONCLUSIONS: The PPL solution is an innovative and easy-to-use submucosal injection solution.

Endocrinological Changes after Anamorelin Administration in Patients with Gastrointestinal Cancer.

Changes in hormone levels in patients with cancer cachexia after anamorelin administration have not been fully investigated. This study aimed to determine how anamorelin affects the endocrine system in patients with gastrointestinal cancer and cachexia. We prospectively enrolled 13 patients and comprehensively investigated their body weight and levels of serum albumin, hemoglobin A1c (HbA1c), and hormones before (week 0) and 3 and 12 weeks after anamorelin administration. The variables were evaluated at week 3 in 9 patients and at week 12 in 5 patients. At week 3, anamorelin administration resulted in body weight gain and increased the levels of growth hormone and HbA1c, as well as insulin-like growth factor-1 standard deviation scores (IGF-1 SD scores). At the same time, negative correlations were observed between ΔIGF-1 SD score and Δthyroidstimulating hormone (TSH) and between ΔIGF-1 SD score and Δfree testosterone. ΔBody weight and ΔIGF-1 SD score correlated positively at week 12. These results suggest that TSH and free testosterone levels can be affected 3 weeks after anamorelin administration; however, those variables tend to return to a state of equilibrium, and anabolic effects of anamorelin appear in long-term (≥ 12 weeks) users.

Linked Color Imaging (LCI) Emphasizes the Color Changes in the Gastric Mucosa After Helicobacter pylori Eradication.

BACKGROUND: Diffuse redness is a characteristic endoscopic finding that indicates current infection of Helicobacter pylori, which is reduced after successful eradication. Linked color imaging (LCI) has been reported to improve the visibility of diffuse redness compared to white light imaging (WLI); however, quantitative evaluation has not been reported. AIMS: This study aimed to objectively evaluate the color change of the gastric mucosa after H. pylori eradication. METHODS: Images of the greater curvature of the antrum and corpus were captured, and the sites were biopsied during esophagogastroduodenoscopy (EGD) before and 1 year after eradication. The region of interest (ROI) was set around the biopsied area on the images. The color difference (ΔE) before and after eradication was calculated using the CIE L*a*b* color space. The association between the histological evaluation and the color value of the corresponding ROI was determined. RESULTS: At the antrum, there was no significant color change with either mode. At the corpus, the a* value, which reflected redness, decreased significantly after eradication with both modes (WLI: 41.2 to 36.0, LCI: 37.5 to 25.5); the b* value, reflecting yellowish, decreased with WLI, but increased significantly with LCI (WLI: 44.6 to 41.6, LCI: 23.9 to 29.2). The ΔE was significantly larger with LCI than with WLI (16.5 vs. 8.6). The a* values at the corpus were generally associated with histological neutrophil infiltration. CONCLUSIONS: Quantitative evaluation revealed that LCI emphasizes the change in color of the gastric mucosa due to the reduction in diffuse redness.

Characteristics of Early Gastric Cancer in a Patient with a History of Helicobacter pylori Infection and No History of Eradication Therapy.

Objective The characteristics of gastric cancer in patients with atrophic mucosa and no apparent history of Helicobacter pylori eradication have not been thoroughly investigated. Therefore, this study examined the clinicopathological characteristics of gastric cancer in these patients. Methods We retrospectively examined the endoscopic and pathological characteristics of gastric cancer in patients who underwent endoscopic submucosal dissection. Patients or Materials We divided the patients into 2 groups: those with gastric atrophy and no history of eradication (group A; n =102) and those with a history of eradication (group B; n =161). In group A, patients were further divided into mild atrophy (group C) and severe atrophy (group D) groups, while group B was further divided into those who underwent eradication treatment >5 years ago (group E) and those who underwent eradication 1-5 years ago (group F). Results Group A comprised significantly older individuals (75±8.0 vs. 71±7.5 years old, p <0.001) with a higher frequency of elevated gastric cancer than group B (32.4% vs. 17.4%, p =0.006). Compared with group E, group A was older and had a greater incidence of elevated gastric cancer. The incidence of gastric cancer in the U or M region was lower in group C than in group D. Conclusion Gastric cancer in patients with gastric atrophy and no history of eradication was associated with an older age and higher frequency of elevated-type morphology than in those with a history of eradication.

Clinical significance of gastrointestinal bleeding history in patients who undergo left atrial appendage closure.

Background and Aim: Anticoagulant users with nonvalvular atrial fibrillation (NVAF) sometimes suffer from gastrointestinal bleeding (GIB) and have difficulty continuing the medication. Left atrial appendage closure (LAAC) has been developed for such situations. We aimed to clarify the clinical significance of a history of GIB in comparison to other factors in patients who had undergone LAAC. Methods: From October 2019 to September 2023, patients with NVAF who underwent LAAC at our hospital were enrolled. We investigated the percentage of patients with a history of GIB who underwent LAAC and compared the incidence of post-LAAC bleeding in these patients compared to those with other factors. Results: A total of 45 patients were included. There were 19 patients (42%) with a history of GIB who underwent LAAC. In a Kaplan-Meier analysis, the cumulative incidence of bleeding complications after LAAC was significantly higher in patients with a history of GIB in comparison to patients with other factors. There were eight cases of post-LAAC bleeding in total, and seven cases had GIB. Conclusions: We need to recognize that GIB is a significant complication in patients who undergo LAAC. The management of GIB by gastroenterologists is essential to the success of LAAC.

Differences in color between early gastric cancer and cancer-suspected non-cancerous mucosa on linked color imaging.

Background and study aims Linked color imaging (LCI) can enhance the original color of each area and may useful to detect tumorous lesions during esophagogastroduodenoscopy. However, LCI may also enhance cancer-suspected non-cancerous regional color change. We conducted a retrospective image analysis to investigate the color characteristics of early gastric cancer (EGC) and cancer-suspected non-cancerous mucosa (CSM) in LCI. Methods LCI images of both EGC and CSM were retrospectively collected from the database of the institution. Fifteen endoscopists individually judged each image as EGC or CSM. The color difference between the inside and outside of the lesions was measured by CIE-Lab analysis in both groups and compared. Results A total of 245 LCI images of EGC (169) and CSM (76) were extracted and randomly lined for image collection. The test by the endoscopists showed accuracy, sensitivity, and specificity of 64.0 %, 63.7 %, and 64.0 %, respectively. Although the color difference between EGC and CSM was almost the same (12.5 vs. 12.9, not significant), each parameter of ΔL (bright: -0.3 vs. -2.7, P  < 0.001), Δa (Reddish: 7.2 vs. 9.6, P  = 0.004), and Δb (Yellowish: 6.4 vs. 3.8, P  < 0.001) was significantly different in the groups. The color feature of both positive ΔL and Δb to EGC showed accuracy, sensitivity, and specificity of 54.7 %, 39.6 %, 88.2%, respectively. Conclusions The total color difference was almost the same between EGC and CSM; however, their color tones were different on linked color imaging. Although the color characteristics of EGC had high specificity, they also had low sensitivity.

Erratum: Differences in color between early gastric cancer and cancer-suspected non-cancerous mucosa on linked color imaging.

[This corrects the article DOI: 10.1055/a-1989-6643.].

Postoperative Bleeding Risk after Gastric Endoscopic Submucosal Dissection in Patients Receiving a P2Y12 Receptor Antagonist.

Background/Aims: The safety of gastric endoscopic submucosal dissection (ESD) in users of a P2Y12 receptor antagonist (P2Y12RA) under current guidelines has not been verified. Methods: Patients treated by gastric ESD at Okayama University Hospital between January 2013 and December 2020 were registered. The postoperative bleeding rates of patients (group A) who did not receive any antithrombotic drugs; patients (group B) receiving aspirin or cilostazol monotherapy; and P2Y12RA users (group C) those on including monotherapy or dual antiplatelet therapy were compared. The risk factors for post-ESD bleeding were examined in a multivariate analysis of patient background, tumor factors, and antithrombotic drug management. Results: Ultimately, 1,036 lesions (847 patients) were enrolled. The bleeding rates of group B and C were significantly higher than that of group A (p=0.012 and p<0.001, respectively), but there was no significant difference between group B and C (p=0.11). The postoperative bleeding rate was significantly higher in dual antiplatelet therapy than in P2Y12RA monotherapy (p=0.014). In multivariate analysis, tumor diameter ≥12 mm (odds ratio [OR], 4.30; 95% confidence interval [CI], 1.99 to 9.31), anticoagulant use (OR, 4.03; 95% CI, 1.64 to 9.86), and P2Y12RA use (OR, 3.40; 95% CI, 1.07 to 10.70) were significant risk factors for postoperative bleeding. Conclusions: P2Y12RA use is a risk factor for postoperative bleeding in patients who undergo ESD even if receiving drug management according to guidelines. Dual antiplatelet therapy carries a higher risk of bleeding than monotherapy.

Endoscopic findings of gastric neoplasms in familial adenomatous polyposis are associated with the phenotypic variations and grades of dysplasia.

Patients with familial adenomatous polyposis (FAP) are at increased risk of developing gastric neoplasms. However, endoscopic findings have not been sufficiently investigated. We investigated the phenotypic expression of gastric adenoma (low-grade dysplasia) and gastric cancer (high-grade dysplasia or carcinoma) in patients with FAP and clarified their relationships to endoscopic findings. Of 29 patients with FAP who underwent esophagogastroduodenoscopy between 2005 and 2020, 11 (38%) had histologically confirmed gastric neoplasms, including 23 lesions of gastric adenoma and 9 lesions of gastric cancer. The gastric neoplasms were classified into 3 phenotypes (gastric, mixed, or intestinal type) according to the immunostaining results and evaluated for location (U or M region: upper or middle third of the stomach or L region: lower third of the stomach), color (same as the background mucosa, whitish, or reddish), macroscopic type (elevated, flat, or depressed), background mucosal atrophy (present or absent), fundic gland polyps in the surrounding mucosa (present or absent), and morphologic changes in tumor size. Elevated whitish gastric adenomas were further subdivided by macroscopic type (flat elevated, protruded, or elevated with a central depression) and color (milky- or pinkish-white). The gastric adenomas included gastric (11/23, 48%), mixed (4/23, 17%), and intestinal (8/23, 35%) phenotypes. In contrast, no lesions of gastric cancers showed a gastric phenotype (0/9, 0%), while 5 (56%) and 4 (44%) lesions were intestinal and mixed phenotypes, respectively. Gastric cancers were significantly more likely than gastric adenomas to present as reddish depressed lesions with gastric atrophy. All gastric-type adenomas occurred in non-atrophic mucosa, in mucosa with fundic gland polyps in the periphery, in the U or M region, and as flat elevated or protruded lesions with a milky-white color. Half of the lesions increased in size. Meanwhile, the typical endoscopic features of intestinal-type adenomas included occurrence in the L region and elevated pinkish-white lesions with central depression. None of the intestinal-type adenomas increased in size during the observation period. We believe that these endoscopic features will be useful for the prompt diagnosis and appropriate management of gastric neoplasms in patients with FAP.

Scoring systems for differentiating gastrointestinal stromal tumors and schwannomas from leiomyomas in the stomach.

ABSTRACT: There is no practical predictive model for the diagnosis of gastrointestinal stromal tumors (GISTs). To establish a practical predictive model for the diagnosis of subepithelial lesions in the stomach, we reviewed patients with GISTs (n = 89), schwannomas (n = 7), and leiomyomas (n = 28).The tumor was more frequently found along the gastric cardia in the leiomyoma group (57.1%) than in the GIST/schwannoma group (2.1%, P < .01). Contrast enhancement (57.3% vs 0%, P < .01) and intra-tumoral necrosis (34.4% vs 0.0%, P < .01) were more frequently observed in the GIST/schwannoma group than in the leiomyoma group. On endoscopic ultrasonography, 58.3% of GISTs/schwannomas showed uneven echogenicity, whereas the echogenicity was uneven in 21.4% of leiomyomas (P < .01). There were no differences between the tumor color and the presence or absence of ulcer formation, tumor bleeding, irregularity of the tumor margin, cystic spaces, and hyperechoic spots between the 2 groups. Based on these results, we developed a 2-step diagnostic algorithm for GISTs/schwannomas. The first step comprises 1 endoscopic feature: a cardiac or non-cardiac location. Tumors with a cardiac location were judged as leiomyomas and those with a non-cardiac location were judged as GISTs/schwannomas, with 96.9% sensitivity and 57.1% specificity for GIST/schwannoma diagnosis. The second step comprises a combination of endoscopic (non-cardiac location), radiologic (positive contrast enhancement and intra-tumoral necrosis), and endosonographic (uneven echogenicity) features for a total of 4 points. We assigned 1 point to each feature. Tumors with scores of 2 to 4 were judged as GISTs/schwannomas, with 81.3% sensitivity and 92.9% specificity for GIST/schwannoma diagnosis.Our predictive model will be a practical guide for the management of gastric subepithelial lesions.

Efficacy and safety of endoscopic submucosal dissection for gastric tube cancer: A multicenter retrospective study.

BACKGROUND: Recent improvements in the prognosis of patients with esophageal cancer have led to the increased occurrence of gastric tube cancer (GTC) in the reconstructed gastric tube. However, there are few reports on the treatment results of endoscopic submucosal dissection (ESD) for GTC. AIM: To evaluate the efficacy and safety of ESD for GTC after esophagectomy in a multicenter trial. METHODS: We retrospectively investigated 48 GTC lesions in 38 consecutive patients with GTC in the reconstructed gastric tube after esophagectomy who had undergone ESD between January 2005 and December 2019 at 8 institutions participating in the Okayama Gut Study group. The clinical indications of ESD for early gastric cancer were similarly applied for GTC after esophagectomy. ESD specimens were evaluated in 2-mm slices according to the Japanese Classification of Gastric Carcinoma with curability assessments divided into curative and non-curative resection based on the Gastric Cancer Treatment Guidelines. Patient characteristics, treatment results, clinical course, and treatment outcomes were analyzed. RESULTS: The median age of patients was 71.5 years (range, 57-84years), and there were 34 men and 4 women. The median observation period after ESD was 884 d (range, 8-4040 d). The median procedure time was 81 min (range, 29-334 min), the en bloc resection rate was 91.7% (44/48), and the curative resection rate was 79% (38/48). Complications during ESD were seen in 4% (2/48) of case, and those after ESD were seen in 10% (5/48) of case. The survival rate at 5 years was 59.5%. During the observation period after ESD, 10 patients died of other diseases. Although there were differences in the procedure time between institutions, a multivariate analysis showed that tumor size was the only factor associated with prolonged procedure time. CONCLUSION: ESD for GTC after esophagectomy was shown to be safe and effective.