Diagnostic performance of linked color imaging for gastric cancer by Helicobacter pylori infection status: A subanalysis of the large-scale, multicenter randomized controlled trial LCI-FIND.

BACKGROUND: Linked color imaging (LCI) is a new image enhancement technology that facilitates the recognition of subtle differences in mucosal color. In the large-scale, multicenter randomized controlled trial LCI-FIND, LCI demonstrated good diagnostic performance for the detection of tumor lesions in the upper gastrointestinal tract. The aim of the present study was to exploratively evaluate the diagnostic performance of LCI according to H. pylori infection status as a subanalysis of LCI-FIND trial. METHODS: The patients were randomly allocated to receive white light imaging (WLI) first, followed by LCI (WLI group), or vice versa (LCI group), and the two groups were compared for the detection of tumors. Data from this trial were analyzed by the presence/absence of H. pylori infection and further analyzed by successful or unsuccessful eradication in the H. pylori infection group. RESULTS: The 752 patients in the WLI group and 750 patients in the LCI group who had participated in the LCI-FIND trial were included. In the successful eradication group, more gastric lesions were detected by primary mode in the LCI group than in the WLI group, indicating that more lesions were missed by WLI. Fisher's exact probability test for the comparison of the WLI and LCI groups yielded a p-value of 0.0068, with missed gastric lesions being detected 0.136 times (95% confidence interval: 0.020-0.923), significantly less with LCI than with WLI. CONCLUSION: The current study suggests that LCI should be used for gastric cancer screening, particularly in patients with successful H. pylori eradication.

'Underwater endoscopic mucosal resection with submucosal injection and marking' for superficial non-ampullary duodenal epithelial tumors to achieve R0 resection: a single-center case series.

OBJECTIVES: To describe an endoscopic technique named 'underwater endoscopic mucosal resection (UEMR) with submucosal injection and marking (UEMR-SIM)' and to evaluate the therapeutic characteristics of superficial non-ampullary duodenal epithelial tumors (SNADETs) < 20 mm vis-a-vis classical EMR (CEMR) and UEMR techniques. MATERIALS AND METHODS: This retrospective study included 103 consecutive SNADET patients (103 lesions) who underwent CEMR, UEMR, or UEMR-SIM. The UEMR-SIM procedure included (1) marking and submucosal injection, (2) filling of the duodenal lumen with 0.9% saline, (3) snaring of the lesion, and (4) electrosurgical removal. The procedural outcomes were compared between the UEMR-SIM and other-procedure groups. RESULTS: The en bloc resection rate was significantly higher in the UEMR-SIM group (100%) than in the CEMR group (76.8%) (p = 0.015) but was not statistically different between the UEMR-SIM and UEMR groups (88.0%) (p = 0.236). The R0 resection rate was significantly higher in the UEMR-SIM group (90.9%) than in the UEMR group (48.0%) (p = 0.001) but was not statistically different between the UEMR-SIM and CEMR groups (76.8%) (p = 0.209). CONCLUSIONS: Our study indicates that the proposed method, UEMR-SIM for SNADETs, is feasible to achieve a high R0 resection rate and a potentially low local recurrence rate.

Linked color imaging provides enhanced visibility with a high color difference in upper gastrointestinal neoplasms.

BACKGROUND AND AIM: The aim of this post-hoc analysis in a randomized, controlled, multicenter trial was to evaluate the visibility of upper gastrointestinal (UGI) neoplasms detected using linked color imaging (LCI) compared with those detected using white light imaging (WLI). METHODS: The visibility of the detected UGI neoplasm images obtained using both WLI and LCI was subjectively reviewed, and the median color difference (ΔE) between each lesion and the surrounding mucosa according to the CIE L*a*b* color space was evaluated objectively. Multivariate logistic regression analysis was performed to identify factors associated with neoplasms that were missed under WLI and detected under LCI. RESULTS: A total of 120 neoplasms, including 10, 32, and 78 neoplasms in the pharynx, esophagus, and stomach, respectively, were analyzed in this study. LCI enhanced the visibility 80.9% and 93.6% of neoplasms in pharynx/esophagus and stomach compared with WLI, respectively. LCI also achieved a higher ΔE of enhanced neoplasms compared with WLI in the pharynx/esophagus and stomach. The median WLI ΔE values for gastric neoplasms missed under WLI and later detected under LCI were significantly lower than those for gastric neoplasms detected under WLI (8.2 vs 9.6, respectively). Furthermore, low levels of WLI ΔE (odds ratio [OR], 7.215) and high levels of LCI ΔE (OR, 22.202) were significantly associated with gastric neoplasms missed under WLI and later detected under LCI. CONCLUSION: Color differences were independently associated with missing gastric neoplasms under WLI, suggesting that LCI has an obvious advantage over WLI in enhancing neoplastic visibility.

Highly feasible procedure for laparoscopic transplantation of cell sheets under pneumoperitoneum in porcine model.

INTRODUCTION: Cell sheet technology is one of the most successful methodologies in regenerative medicine. Various applications of cell sheets have been introduced in first-in-human studies in several clinical fields. When transplanting a cell sheet into internal organs, a relatively large incision is required for delivery due to difficulty handling the sheet. We developed a laparoscopic delivery procedure for safe and easy transplantation of cell sheets in a porcine model. METHODS: Pneumoperitoneum was established by inflation with CO2. First, to increase the strength during handling, fibrin was sprayed onto the surface of the cell sheet, and then a myoblast sheet was placed onto the newly developed carrier. The sheets were pinched with laparoscopic forceps to insert into the abdominal cavity through the laparoscopic port. Myoblast sheets were then applied to the surface of the liver, colon, small intestine, and stomach, and procedure times were measured. At three days post transplantation, a histopathological examination was performed to confirm engraftment of the sheet. The function and engraftment were also analyzed in a duodenal endoscopic submucosal dissection (ESD) model. RESULTS: The fibrin-processed myoblast sheet was able to be managed with conventional laparoscopic forceps without breaking. Despite the drastic change in air pressure by passing through the laparoscopic port, the sheets suffered no apparent damage. The transplantation procedure times did not markedly differ among transplant sites. A histopathological examination revealed thin-layered, desmin-positive cells at each transplant site. With transplantation following ESD, the engrafted myoblast sheets effectively prevented delayed perforation. CONCLUSIONS: Our procedure is simple, and the system involves a carrier made of medically fit silicon, commercially available fibrin glue and conventional laparoscopic forceps. Our procedure is a powerful tool for laparoscopical cell sheet transplantation.

Linked Color Imaging Focused on Neoplasm Detection in the Upper Gastrointestinal Tract : A Randomized Trial.

BACKGROUND: Linked color imaging (LCI) is a new image-enhanced endoscopy technique that allows users to recognize slight differences in mucosal color. OBJECTIVE: To compare the performance of LCI with white light imaging (WLI) in detecting neoplastic lesions in the upper gastrointestinal tract. DESIGN: A controlled, multicenter trial with randomization using minimization. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000023863). SETTING: 16 university hospitals and 3 tertiary care hospitals in Japan. PATIENTS: 1502 patients with known previous or current cancer of the gastrointestinal tract and undergoing surveillance for gastrointestinal cancer. INTERVENTION: WLI followed by LCI examination (WLI group) or LCI followed by WLI examination (LCI group). MEASUREMENTS: Diagnosis of 1 or more neoplastic lesions in the pharynx, esophagus, or stomach in the first examination (primary outcome) and 1 or more neoplastic lesions overlooked in the first examination (secondary outcome). RESULTS: 752 patients were assigned to the WLI group and 750 to the LCI group. The percentage of patients with 1 or more neoplastic lesions diagnosed in the first examination was higher with LCI than with WLI (60 of 750 patients or 8.0% [95% CI, 6.2% to 10.2%] vs. 36 of 752 patients or 4.8% [CI, 3.4% to 6.6%]; risk ratio, 1.67 [CI, 1.12 to 2.50; P = 0.011]). The proportion with overlooked neoplasms was lower in the LCI group than in the WLI group (5 of 750 patients or 0.67% [CI, 0.2% to 1.6%] vs. 26 of 752 patients or 3.5% [CI, 2.3% to 5.0%]; risk ratio, 0.19 [CI, 0.07 to 0.50]). LIMITATION: Endoscopists were not blinded. CONCLUSION: LCI is more effective than WLI for detecting neoplastic lesions in the pharynx, esophagus, and stomach. PRIMARY FUNDING SOURCE: Fujifilm Corporation.

Establishment of an in-vivo porcine delayed perforation model after duodenal endoscopic submucosal dissection.

OBJECTIVES: Duodenal endoscopic submucosal dissection (ESD) for superficial non-ampullary duodenal epithelial tumors has a significant incidence rate of delayed perforation. Although several methods have been proposed to prevent delayed perforation, the most appropriate methods remain unclear. Currently, there is no appropriate animal model to validate methods for preventing duodenal delayed perforation. This study aimed to establish an in-vivo porcine delayed perforation model after duodenal submucosal dissection. METHODS: Two porcine models underwent either ESD or surgical submucosal dissection. In the surgical dissection model, an inverted duodenal mucosa was resected with electrosurgical energy. In the ESD model, a gauze was placed behind the duodenum with grasped transverse part to improve endoscopic maneuverability. The mucosal defects after dissection were treated with omental coverage without suture in both models. All models were euthanized 0-5 days after procedure. Body weight; resection size; procedure dissection time; presence of intraoperative perforation and delayed perforation; and adhesion score were assessed. RESULTS: There were no significant differences in body weight and adhesion score between the two models. Resection size was significantly larger in the surgical dissection models than in the ESD models (19 mm vs 14.3 mm, P < 0.01). Procedure time was significantly longer in the ESD models than in the surgical models (45.2 minutes vs 4.5 minutes, P < 0.01). Delayed perforation rates in the surgical dissection models and the ESD models were 0% (0/5) and 100% (5/5), respectively (P < 0.01). CONCLUSIONS: This study indicated that our in-vivo porcine duodenal ESD model is beneficial to evaluate a prevention strategy for delayed perforation.

Comprehensive Prospective Analysis of the Factors Contributing to Aspiration Pneumonia Following Endoscopic Submucosal Dissection in Patients with Early Gastric Neoplasms.

Endoscopic submucosal dissection (ESD) has become the first-line treatment for early gastric neoplasms; however, a subset of patients treated by this method develop aspiration pneumonia. We conducted a comprehensive prospective analysis of the factors contributing to post-ESD aspiration pneumonia in early gastric neoplasms in this study, with special focus on whether pre-treatment oral care can prevent aspiration pneumonia. Sixty-one patients who underwent ESD for gastric neoplasms were randomly assigned to the oral care or control groups. ESD was performed under deep sedation. Of 60 patients whose data were available for analysis, 5 (8.3%) experienced pneumonia confirmed either by chest radiography or computed tomography. Although no difference in the rate of pneumonia was found between the control and oral care groups, the post-oral care bacteria count was significantly higher in the saliva of patients who developed pneumonia compared to those without pneumonia. In addition, the presence of vascular brain diseases and the dose of meperidine were also significantly associated with the occurrence of pneumonia. These results suggest that the number of oral bacteria as well as pre-existing vascular brain diseases and high-dose narcotics can affect the incidence of post-ESD pneumonia.

Early stage signet ring cell carcinoma of the colon examined by magnifying endoscopy with narrow-band imaging: a case report.

BACKGROUND: Signet ring cell carcinoma of the colon and rectum is rare, and most cases are detected at an advanced stage. We present a case of primary signet ring cell carcinoma detected at an early stage by magnifying endoscopy with narrow-band imaging (NBI) and crystal violet staining. CASE PRESENTATION: A 73-year-old man visited our hospital for screening colonoscopy. Six years previously, he had undergone endoscopic submucosal dissection (ESD) for early gastric cancer. The pathological diagnosis was a well-differentiated adenocarcinoma, invading into the mucosa without lymphovascular invasion. Colonoscopy revealed a flat elevated lesion with a slightly depressed area, 20 mm in diameter, in the cecum. Further, magnifying endoscopy with NBI revealed that the surface pattern was slightly irregular and microvessels had a regular diameter and distribution in the margin of the lesion, but in the central part of the lesion, irregularity in the tumor surface pattern and form as well as in the diameter and distribution of microvessels was noted. Additionally, due to mucus, avascular areas were also observed. Magnifying endoscopy combined with 0.05 % crystal violet staining showed IIIL and VI pit patterns in the margin of the lesion, and a VI pit pattern in the central part of the lesion; however, due to mucus exudate, this finding could not be established with certainty. The lesion was successfully removed en bloc using ESD without complications. The tumor was composed mainly of signet ring cell carcinoma, partially mixed with moderately differentiated (tub2) and well-differentiated (tub1) adenocarcinomas. The tumor cells infiltrated 250 µm into the submucosal layer and involved lymphatic vessels. Therefore, the patient underwent an additional laparoscopic ileocecal resection, and the resected specimen revealed no residual carcinoma or lymph node metastasis. CONCLUSION: In this case report, we present a case of primary signet ring cell carcinoma detected at an early stage and identified by magnifying endoscopy with NBI and crystal violet staining.

Advantages of fecal lactoferrin measurement during granulocyte and monocyte adsorptive apheresis therapy in ulcerative colitis.

BACKGROUND: Fecal lactoferrin has been introduced as a useful tool for the diagnosis and monitoring of inflammatory bowel disease (IBD). The aim of this study was to assess if fecal lactoferrin can be employed to predict or estimate the effect of granulocyte and monocyte adsorptive apheresis (GMA) in ulcerative colitis (UC). METHODS: This was a prospective study involving 21 patients with UC. Patients with moderately-to-severely active UC who were scheduled to undergo GMA were recruited. Changes in fecal lactoferrin concentration were compared between the GMA-responder and -nonresponder groups. RESULTS: In the GMA-responder group, fecal lactoferrin significantly increased 1 week after the introduction of GMA and then significantly decreased after GMA sessions. Fecal lactoferrin concentrations were significantly higher in the GMA-responder group than in the GMA-nonresponder group at 1 and 2 weeks after the introduction of GMA. Multivariate logistic regression analysis revealed that fecal lactoferrin concentration 1 week after the introduction of GMA was the most contributing factor for the effectiveness of GMA in patients with UC. CONCLUSIONS: In the GMA-responder group, fecal lactoferrin concentration significantly increased 1 week after the introduction of GMA. Fecal lactoferrin may be beneficial for predicting clinical response of GMA in patients with UC at an early stage of GMA treatment.

Clinical Characteristics of Patients with Gastroesophageal Reflux Disease Refractory to Proton Pump Inhibitors and the Effects of Switching to 20 mg Esomeprazole on Reflux Symptoms and Quality of Life.

BACKGROUND Refractory gastroesophageal reflux disease (GERD) may deteriorate patient quality of life (QOL) despite proton pump inhibitor (PPI) therapy. MATERIAL AND METHODS Nineteen Japanese institutions were surveyed to determine the clinical characteristics and QOL of patients with refractory GERD. Those patients treated with a conventional PPI were switched to 20 mg esomeprazole for 4 weeks. Symptoms and QOL were assessed using Global Overall Symptom and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires at baseline and at 2 and/or 4 weeks of esomeprazole treatment. RESULTS Of 120 patients who completed the survey, 58 (48.3%) had refractory GERD. Of these, 69.0% were aged ≥ 65 years, 79.3% were prescribed a PPI at a standard or high dose, and 22.4% were prescribed a PPI together with another drug. After switching to esomeprazole, patients reported significant improvements in heartburn, acid regurgitation, and excessive belching at 2 weeks using a symptom diary, as well as the total score, reflux, abdominal pain, and indigestion, which were assessed using the GSRS at 4 weeks. CONCLUSIONS About half of Japanese patients with GERD may be refractory to conventional PPIs. Their reflux-related symptoms are often severe and may impair QOL. Switching to esomeprazole could be used to improve their symptoms and QOL.

Per-oral endoscopic myotomy: emerging indications and evolving techniques.

Esophageal achalasia is a benign esophageal motility disorder resulting from an impaired relaxation of the lower esophageal sphincter. The principles of treatment involve disruption of the sphincter at the esophagogastric junction. Treatment techniques include balloon dilatation, botulinum toxin injection, and surgical myotomy. In 2008, per-oral endoscopic myotomy (POEM) was introduced by Inoue et al. as an endoscopic myotomy with no skin incision. The procedure has been well accepted and widely applied owing to its minimal invasiveness and high cure rates. Moreover, there have been discussions on wider indications for POEM and new technical developments have been reported. The present article reviews the historical background and present status of POEM, as well as future prospects for its application in the treatment of esophageal achalasia.

Bamboo joint-like appearance of the stomach: a stable endoscopic landmark for Crohn's disease regardless of anti-tumor necrosis factor alpha treatment.

BACKGROUND: Bamboo joint-like appearance is a common yet easy-to-miss endoscopic finding in the stomach of patients with Crohn's disease (CD). Bamboo joint-like appearance (BJA) is characterized by swollen longitudinal folds transversed by erosive fissures or linear furrows. However, whether BJA is observed during the remission stage of CD and during the active stage is unclear. In particular, the relationship between the course of BJA and anti-tumor necrosis factor (TNF) α therapy has not been studied. We aimed to evaluate the course of BJA in CD patients treated with anti-TNF α therapy. MATERIAL AND METHODS: We examined 22 CD patients who underwent esophagogastroduodenal endoscopy before undergoing anti-TNF α treatment. We evaluated the changes in BJA, clinical activity using the CD activity index (CDAI), and endoscopic activity using the simple endoscopic score for CD (SES-CD) from 6 months to 1 year after anti-TNF α therapy. RESULTS: Fifteen of 22 patients (68.1%) presented with BJA in the stomach, 13 of whom received follow-up esophagogastroduodenal endoscopy after anti-TNF α therapy. The mean CDAI and SES-CD scores significantly improved after anti-TNF α therapy (P<0.01). Despite the marked improvements in clinical and endoscopic findings, the BJA of the stomach remained unchanged in all the patients. CONCLUSIONS: The findings indicate that BJA is frequently observed in the stomach of CD patients, regardless of whether the patient has active disease or is in remission, even after anti-TNF α therapy. Thus, BJA may be a stable endoscopic landmark in CD.

Colonic intussusception after endoscopic mucosal resection successfully managed by endoscopic procedure.

Adult-onset intussusception, particularly associated with colonoscopy, is extremely rare. A 78-year-old man, referred to our hospital for colonic endoscopic mucosal resection (EMR), experienced subsequent dull abdominal pain, as well as elevated peripheral blood leukocytosis and C-reactive protein levels. Abdominal computed tomography (CT) revealed a colocolonic intussusception at the hepatic flexure. Emergency colonoscopy revealed ball-like swollen mucosa distal to the EMR site of the ascending colon. The mucosa was intact without necrosis. The endoscopic approach was able to temporarily release the intussusception. A transanal drainage tube was inserted through the endoscope to prevent relapse. Both CT and colonoscopy showed release of the intussusception. Our case underscores the importance of considering colocolonic intussusception in post-colonoscopy abdominal pain, advocating for endoscopic management after excluding mucosal necrosis.

Characteristics and Risk Factors of Delayed Perforation in Endoscopic Submucosal Dissection for Early Gastric Cancer.

(1) Background: Delayed perforation after gastric endoscopic submucosal dissection (ESD) for early gastric cancer is a relatively uncommon and serious complication that sometimes requires emergency surgery. This study aimed to determine the clinicopathological features, risk factors, and appropriate management strategies for delayed perforation. (2) Methods: This study included 735 patients with 791 lesions who underwent ESD for early gastric cancer at a single institution between July 2009 and June 2019. We retrospectively compared the clinical features of patients with and without delayed perforations. (3) Results: The incidence of delayed perforations was 0.91%. The identified risk factors included a postoperative stomach condition and histopathological ulceration. A comparison between delayed and intraoperative perforations revealed a postoperative stomach condition as a characteristic risk factor for delayed perforation. Patients with delayed perforation who avoided emergency surgery tended to exhibit an earlier onset of symptoms such as abdominal pain and fever. No peritoneal seeding following delayed perforation was observed for any patient. (4) Conclusions: A postoperative stomach condition and histopathological ulceration were risk factors for delayed perforation. Delayed perforation is a significant complication that requires careful monitoring after gastric ESD for early gastric cancer, particularly in patients with postoperative gastric conditions.

18F-fluorodeoxyglucose positron emission tomography/computed tomography parameters are associated with histological outcomes in superficial esophageal squamous cell carcinoma.

Endoscopic submucosal dissection is a standard treatment for early esophageal squamous cell carcinoma. However, submucosal or lymphovascular invasion increases the risk of lymph node metastasis. Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters are associated with prognosis in patients with advanced esophageal squamous cell carcinoma, the utility of FDG PET/CT in diagnosing superficial esophageal carcinoma remains unclear. This study aimed to investigate the association between FDG PET/CT parameters and histopathological findings in superficial esophageal carcinoma. Fifty-three patients with superficial esophageal cancer who underwent FDG PET/CT scans before undergoing interventions were retrospectively analyzed. The maximal standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis were significantly higher in the cases with submucosal invasion (T1b) compared with those confined to the muscularis mucosa (T1a). In contrast, classification of intrapapillary capillary loops patterns with magnifying endoscopy did not yield statistical differences between T1a and T1b. Multivariable analysis revealed that SUVmax was the only independent predictor of submucosal and lymphovascular invasion. This study demonstrated that SUVmax may be useful in predicting submucosal and lymphovascular invasion. Thus, the value of SUVmax may guide clinical decision-making in superficial esophageal squamous cell carcinoma.

Long-term prognosis and DNA damage status after oral mucosal epithelial cell sheet transplantation following esophageal endoscopic submucosal dissection for squamous cell carcinoma: A case series.

Autologous oral mucosal epithelial cell sheet (AOMECS) transplantation has recently been applied in human patients to prevent postprocedural stenosis following endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma. However, the long-term safety of AOMECS transplantation remains unclear. We evaluated the long-term outcomes of 10 patients who participated in a clinical trial of AOMECS transplantation after esophageal ESD. Additionally, we assessed the local DNA damage response in the esophageal epithelium using p53 binding protein 1 (53BP1) immunofluorescence in post-AOMECS biopsy specimens. The median follow-up period was 118.5 months (range: 46-130 months). Two patients developed primary esophageal cancer near the AOMECS site and successfully underwent additional ESD. One patient developed lymph node metastasis and underwent chemotherapy. None of the patients died from the original disease, although one patient died from unrelated causes. The rate of abnormal 53BP1 nuclear foci, indicative of increased genome instability, increased with the progression of neoplasia in patients post AOMECS. Our case series suggests that AOMECS transplantation provides an acceptable long-term prognosis and 53BP1 foci may serve as a useful marker for assessing DNA instability in the post-AOMECS esophageal epithelium.

Significance of P53-Binding Protein 1 as a Novel Molecular Histological Marker for Hypopharyngeal Squamous Neoplasms.

The DNA damage response protein p53-binding protein 1 (53BP1) accumulates and forms foci at double-strand DNA breaks, indicating the extent of DNA instability. However, the potential role of 53BP1 as a molecular biomarker for hypopharyngeal squamous cell carcinoma (HPSCC) diagnosis remains unknown. Here, we evaluated the potential of immunofluorescence-based analysis of 53BP1 expression to differentiate the histology of hypopharyngeal neoplasms. A total of 125 lesions from 39 surgically or endoscopically resected specimens from patients with HPSCC was histologically evaluated. 53BP1 expression in the nucleus was examined using immunofluorescence. The number of 53BP1 nuclear foci increased with the progression from non-tumorous to low-grade dysplasia, high-grade dysplasia, and squamous cell carcinoma. Unstable 53BP1 expression served as an independent factor for distinguishing lesions that required intervention. Colocalization of 53BP1 foci in proliferating cells, as assessed by Ki67, was increased in tumors ≥ 1000 µm in depth compared to those <1000 µm in depth at the tumor surface. Hence, the expression patterns of nuclear 53BP1 foci were associated with the progression of hypopharyngeal neoplasms. These findings suggest that 53BP1 could serve as an ancillary marker to support histological diagnosis and predict the factors that influence prognosis in patients with HPSCC.

A first-in-human clinical study of laparoscopic autologous myoblast sheet transplantation to prevent delayed perforation after duodenal endoscopic mucosal dissection.

BACKGROUND: The detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) has recently been increasing. Large tumors may contain malignant lesions and early therapeutic intervention is recommended. Endoscopic mucosal dissection (ESD) is considered a feasible treatment modality, however, the anatomical and physiological characteristics of the duodenum create a risk of postoperative perforation after ESD. METHODS: To explore whether myoblast sheet transplantation could prevent delayed perforation after ESD, a first-in-human (FIH) clinical trial of laparoscopic autologous myoblast sheet transplantation after duodenal ESD was launched. Autologous myoblast sheets fabricated from muscle tissue obtained seven weeks before ESD were transplanted laparoscopically onto the serous side of the ESD. The primary endpoints were the onset of peritonitis due to delayed perforation within three days after surgery and all adverse events during the follow-up period. RESULTS: Three patients with SNADETs ≥ 20 mm in size underwent transplantation of a myoblast sheet onto the serous side of the duodenum after ESD. In case 1, The patient's postoperative course was uneventful. Endoscopy and abdominal computed tomography revealed no signs of delayed perforation. Despite incomplete mucosal closure in case 2, and multiple micro perforations during ESD in case 3, cell sheet transplantation could prevent the postoperative massive perforation after ESD, and endoscopy on day 49 after transplantation revealed no stenosis. CONCLUSIONS: This clinical trial showed the safety, efficacy, and procedural operability of this novel regenerative medicine approach involving transplanting an autologous myoblast sheet laparoscopically onto the serosa after ESD in cases with a high risk of delayed perforation. This result indicates the potential application of cell sheet medicine in treating various abdominal organs and conditions with minimal invasiveness in the future. TRIAL REGISTRATION: jRCT, jRCT2073210094. Registered November 8 2021, https://jrct.niph.go.jp/latest-detail/jRCT2073210094 .

Photodynamic Diagnosis for the Identification of Intestinal-Type Gastric Cancers and High-Grade Adenomas.

Gastric cancer is the second most common cancer in Japan. The incidence of gastric cancer remains high owing to the increase in the elderly population. Endoscopy outperforms radiography in identifying early gastric cancer (EGC). Furthermore, image-enhanced endoscopy (IEE) has been developed and implemented worldwide in clinical practice. Magnifying IEE images can help to visualize the microvascular pattern and microstructure architecture, which is used for the characterization of EGC. However, accurate endoscopic diagnosis requires the experience and skill of endoscopists, making an objective and simple diagnostic method desirable. In this retrospective study, we investigated the diagnostic yield of 5-aminolevulinic acid (5-ALA)-mediated photodynamic diagnosis (PDD) for identifying gastric cancers and high-grade adenomas. In total, 52 lesions from 43 patients were ultimately included in the study. We detected 5-ALA-mediated protoporphyrin IX fluorescence in 45 of the 52 lesions that were initially intended for PDD, resulting in a detection rate of 86.5%, whereas each signet ring cell carcinoma was negative using 5-ALA PDD. In eight of the patients with multiple lesions, 17 lesions were identified using 5-ALA PDD. Again, we took biopsies from six areas that we suspected as new lesions. While 4 lesions were gastric neoplasms resected by endoscopic submucosal dissection, two other lesions were normal. Preoperative 5-ALA-PDD could provide additional diagnostic yields to detect such multiple lesions simultaneously. No severe adverse events were observed. Prospective multicenter studies are warranted to confirm the usefulness of 5-ALA PDD for EGC identification.