Endoscopic hand suturing for mucosal defect closure after gastric endoscopic submucosal dissection may reduce the risk of postoperative bleeding in patients receiving antithrombotic therapy.

OBJECTIVES: Endoscopic hand suturing (EHS) is expected to decrease the risk of post-endoscopic submucosal dissection (ESD) bleeding by closing mucosal defects. We investigated the efficacy of EHS after gastric ESD in patients with antithrombotic agents. METHODS: In this prospective single-arm trial, patients taking antithrombotic agents for cardiovascular disease, arrhythmia, cerebrovascular disease and/or peripheral arterial disease and having <3-cm gastric neoplasms were recruited. The mucosal defects after ESD were closed by EHS in which the needle was delivered through an overtube, and the mucosal rim of the defect was continuously sutured in a linear fashion by manipulating the needle grasped with the needle holder, followed by cutting the remnant suture and retrieval of the needle. The primary endpoint was the incidence of postoperative bleeding within 4 weeks after ESD. RESULTS: Twenty-two lesions in 20 patients (continuing antiplatelet agents in 11, anticoagulant agents in eight, both in one) underwent ESD followed by EHS. All defects (median size, 30 mm; range, 12-51 mm) were completely closed by EHS and remained closed on postoperative day 3. The median number of stitches was six (range, 4-8) and median suturing time was 36 (range, 24-60) min. There were no adverse events during/after EHS or postoperative bleeding. CONCLUSIONS: Postoperative bleeding was not observed in patients taking antithrombotic agents without perioperative cessation. EHS appears to be useful for prevention of post-gastric ESD bleeding in high-risk patients. (Clinical registration number: UMIN000024184).

Efficacy of a new image-enhancement technique for achieving hemostasis in endoscopic submucosal dissection.

BACKGROUND AND AIMS: Hemostasis during endoscopic submucosal dissection (ESD) can sometimes be challenging and stressful for the endoscopist. Therefore, we aimed to assess the usefulness of dual red imaging (DRI), a new image enhancement technique that uses 3 wavelengths (540, 600, and 630 nm) to visualize bleeding points and to examine the efficacy of DRI in shortening the time required to achieve hemostasis (hemostasis time) during ESD. METHODS: DRI and white-light imaging (WLI) were used alternately for managing 378 bleeding events in 97 patients undergoing ESD. Hemostasis time for each hemostasis event was measured. Using portable eye-tracking glasses, 4 experienced endoscopists were shown random videos of intraoperative bleeding during ESD (20 cases each on WLI and DRI) and identified the bleeding point in each video. The mean distances of eye movement per unit of time until the bleeding point were identified in each video and compared between the WLI and DRI groups. RESULTS: Average hemostasis time was significantly shorter in the DRI group. The mean distance of eye movement was significantly shorter in the DRI group than in the WLI group for all endoscopists. CONCLUSIONS: DRI can offer useful images to help in clearly detecting bleeding points and in facilitating hemostasis during ESD. It is feasible and may help in successfully performing ESD that is safer and faster than WLI. (Clinical trial registration number: UMIN000018309.).

Salvage endoscopic submucosal dissection for incompletely resected esophageal or gastric neoplasms (case series).

Background and study aims Given that positive lateral margins indicate possible residual carcinoma, salvage endoscopic submucosal dissection (ESD) should be considered for curative therapy. Presence of submucosal fibrosis, however, makes the procedure difficult to perform. We present our case series to discuss the feasibility of salvage ESD and the timing of the procedure.

Endoscopic suturing promotes healing of mucosal defects after gastric endoscopic submucosal dissection: endoscopic and histologic analyses in in vivo porcine models (with video).

BACKGROUND AND AIMS: Endoscopic suturing of mucosal defects after endoscopic submucosal dissection (ESD) is expected to prevent postoperative adverse events. We aimed to endoscopically and histologically evaluate the healing process of post-ESD mucosal defects closed with endoscopic hand suturing (EHS) in in vivo porcine models. METHODS: Twelve mucosal defects (2 cm in size) were created in 2 pigs (6 defects per pig). Initially, 2 defects were created: one was closed with EHS (sutured group) and the other was kept open (control group). On postoperative days (PODs) 7 and 14, 2 additional defects were created in each session, and they were treated in the same manner as in the initial procedure. On POD 21, the entire stomach, with the 6 lesion sites, was extracted for histologic evaluation after endoscopic observation. RESULTS: Endoscopically, all sutured sites remained closed in all sessions (PODs 7, 14, and 21). Histologically, on POD 14, the epithelium and muscularis mucosae were appropriately connected. The mucosae were covered with the epithelium without inversion of the mucosal edge in the sutured group, whereas the ulcer bed was exposed in the control group. Furthermore, the degree of neovascularity and fibroblasts in the submucosa was smaller in the sutured group than that in the control group. CONCLUSIONS: Our findings suggest that endoscopic suturing promotes healing of post-ESD mucosal defects histologically in in vivo porcine models. Thus, endoscopic mucosal closure after ESD might be clinically useful for the prevention of delayed perforation/bleeding if secure suturing is performed endoscopically.

Feasibility of endoscopic submucosal dissection for colorectal neoplasia at anastomotic sites: a retrospective study.

BACKGROUND: Metachronous colorectal lesions sometimes occur at anastomotic sites following colorectal surgery, which increases the risk of developing colorectal cancer. However, these lesions are difficult to treat even with minimally invasive methods such as endoscopic submucosal dissection (ESD). Thus, we aimed to evaluate the outcomes of ESD for colorectal lesions at anastomotic sites following colorectal surgery. METHODS: We retrospectively investigated 11 patients with post-surgical colorectal lesions at anastomotic sites who later underwent ESD from May 2010 to April 2019 at Keio University Hospital, Tokyo, Japan. We examined the patients' background (tumor location, macroscopic type, tumor size, histological type, and depth of invasion) and treatment outcomes (procedure duration, en bloc resection rate, R0 resection rate, and adverse events). RESULTS: The patients' mean age was 66 years. There were two lesions in the transverse colon, six in the rectum, one in the anal canal, and two in the ileal pouch. The median tumor size was 25 mm. The macroscopic types were the protruded type (1 lesion) and the flat or depressed type (10 lesions). The pathological diagnoses were adenoma (4 lesions), intramucosal cancer (corresponding to high-grade dysplasia) (6 lesions), and muscularis propria cancer (1 lesion). The median procedure duration was 50 min; en bloc resection rate was 88.9% and R0 resection rate was 66.7%. The only adverse event was delayed post-ESD bleeding. CONCLUSIONS: A high en bloc resection rate without perforation was achieved with ESD for lesions at anastomotic sites. Although ESD for lesions at anastomotic sites is a technically challenging procedure because of severe submucosal fibrosis, this approach could prevent the need for repeated surgical resection.

How I do it: Endoscopic diagnosis for superficial non-ampullary duodenal epithelial tumors.

There are no reports on detailed endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADET) except for relatively small case series. Herein, we conducted a prospective observational study to investigate the relationship between endoscopic findings and histopathological diagnosis of SNADET. A total of 163 SNADET diagnosed using magnified endoscopic examination with image-enhanced endoscopy (IEE-ME) were prospectively registered in this study. We investigated location, size, macroscopic type, color, and IEE-ME findings including surface structure (closed- or open-loop) and presence of white opaque substance (WOS) in SNADET. We analyzed association between these findings and histopathological diagnosis of SNADET based on the Vienna classification (VCL) using logistic regression analysis. In univariate analysis, lesion size, superficial structure, and WOS deposition showed statistical significance, and the oral side of the lesion location showed statistical tendency for association with VCL C4/5. In multivariate analysis, lesion size (odds ratio [OR], 2.92; 95% CI, 1.94-4.39; P < 0.05) and negative WOS (OR, 5.59; 95% CI, 1.72-18.1; P < 0.05) were significantly associated with VCL C4/5 lesions. Superficial structures with a closed-loop pattern on the surface showed statistical tendency for predicting VCL C4/5 lesions (OR, 2.15; 95% CI, 0.86-5.37; P = 0.10). Based on these findings, we concluded that negative WOS by IEE-ME and lesion size were independent predictors of VCL C4/5 SNADET. These factors may help us to understand of pathophysiology of SNADET and to select appropriate therapeutic strategies.

Feasibility study comparing underwater endoscopic mucosal resection and conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumor < 20 mm.

BACKGROUND AND AIM: Underwater endoscopic mucosal resection (UEMR) has been reported as an alternative to conventional EMR for superficial non-ampullary duodenal epithelial tumors (SNADET). However, the detailed outcomes are unclear. This study aimed to compare the clinical outcomes between UEMR and EMR for SNADET <20 mm. PATIENTS AND METHODS: This is a retrospective observational study using a prospective maintained database. From November 2017 to December 2018, 104 consecutive cases of attempted UEMR for SNADET <20 mm were prospectively allocated. A total of 240 cases of attempted EMR were chosen as historical controls. We compared technical success rate, defined as the resection rate without conversion to ESD; en bloc resection rate; R0 resection rate; and adverse event rate. Next, multivariate analyses were constructed to identify predictors of conversion to ESD, piecemeal resection, and RX or R1 (RX/R1) resection. RESULTS: Technical success rate of UEMR was significantly higher than that of EMR (87% and 70%, P < 0.01). En bloc resection and R0 resection rates of UEMR were significantly lower than those of EMR (en bloc resection: 87% vs 96%, P < 0.01; R0 resection: 67% vs 80%, P = 0.05). Concerning adverse events, there were no significant differences. In multivariate analyses, attempted EMR, lesion size and depressed type were independent predictors of conversion to ESD. Attempted UEMR was an independent predictor of piecemeal resection and RX/R1 resection. CONCLUSION: The present study indicated that UEMR could be a feasible endoscopic resection method for SNADET (UMIN000025442).

Predictors of technical difficulty with duodenal ESD.

Background and study aims Duodenal endoscopic submucosal dissection (ESD) is still considered technically challenging; however, few studies have objectively analyzed predictors of the technical difficulty. Therefore, the aim of the current study was to elucidate predictors of the technical difficulty of duodenal ESD. Patients and methods This was a retrospective observational study. From June 2010 to June 2017, a total of 174 consecutive patients with superficial duodenal epithelial neoplasia who underwent ESD were included in this study. We tried to identify predictors for technical difficulty of ESD by defining technical difficulty as either procedure time > 100 minutes or intraprocedural perforation. Moreover, we constructed a scoring system consisting of factors that were significant in the multivariate analysis. Results The proportion of patients with technical difficulty was 34.5 %. In the multivariate analysis, lesion location in flexural part [odds ratio (OR), 2.61; 95 % confidence interval (CI), 1.02 - 6.68], larger lesion size (> 40 mm) (OR, 5.26; 95% CI, 2.15 - 12.9), and occupied circumference > 50 % of the duodenum (OR, 5.80; 95 % CI, 1.83 - 18.4) were associated with technical difficulty. Conclusion A lesion location in flexural part, lesion size >40 mm and occupied circumference > 50 % were risk factors for technical difficulty of duodenal ESD.

Dual red imaging: a novel endoscopic imaging technology visualizing thick blood vessels in the gastrointestinal wall.

Background Dual red imaging (DRI), a novel image-enhanced endoscopy (IEE) technology, has the potential to improve the visibility of blood vessels in deeper tissue using 600 nm and 630 nm wavelength lights in the red band. Aim To confirm the feasibility of DRI in visualization of vessels in deeper tissue and identify pathologically the features of blood vessels visualized by DRI. Methods Study 1: visibility of blood vessels was assessed by five observers in 137 pairs of DRI and white light imaging (WLI) images. The scores for the visibility of thick blood vessels were measured for randomized images and compared with the scoring template as a reference. The difference in visibility score between DRI and WLI was compared in each pair of images. Study 2: blood vessels detected only by DRI were examined pathologically using two pig stomachs. Results Study 1: The mean visibility scores of DRI and WLI for each observer were 1.69 - 2.26 and 1.31 - 1.67, respectively. The mean difference in visibility score and 95 % confidence interval for the five observers was 0.59 [0.46 - 0.72], 0.54 [0.40 - 0.68], 0.34 [0.18 - 0.49], 0.51 [0.36 - 0.66], and 0.71 [0.54 - 0.88]. The visibility was statistically significantly better in DRI than in WLI for all observers ( P  < 0.0001). Study 2: three blood vessels were observed only by DRI. All of these blood vessels were located at a depth of 1000 - 1500 µm from the mucosal surface. The diameter of these blood vessels exceeded 80 - 200 µm. Conclusions DRI can feasibly detect thick blood vessels in the deep mucosa or submucosa of the gastrointestinal tract.

Haemostasis treatment using dual red imaging during endoscopic submucosal dissection: a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Patients scheduled to undergo oesophageal, gastric and colorectal endoscopic submucosal dissection (ESD) are to be investigated to verify the efficacy of dual red imaging (DRI) for establishing haemostasis during ESD. METHODS AND ANALYSIS: The trial is designed as a multicentre, open-label randomised, parallel-group, controlled intervention study. Registered patients will be randomly assigned to DRI and white light imaging (WLI) groups. In the DRI group, the mucosal incision and submucosal dissection will be performed by WLI, and haemostasis will be managed by DRI when bleeding occurs. In the WLI group, the mucosal incision and submucosal dissection are to be performed by WLI and the haemostasis management is to be performed by WLI. The primary endpoint is the time from the recognition of bleeding up to the achievement of complete haemostasis (haemostasis time). The secondary endpoints are the operation time, the proportion of cases in which perforation occurs, and the psychological stress experienced by the endoscopist during haemostasis treatment. ETHICS AND DISSEMINATION: This trial was approved by the Keio University Review Board for Clinical Trials (5 December 2016). DISCUSSION: This will be the first multicentre collaborative research using DRI for haemostasis treatment during ESD. When the safety and simplicity of DRI as a treatment for haemostasis during ESD can be proven, the ESD procedure can be simplified and disseminated more widely in clinical practice. TRIAL REGISTRATION NUMBER: UMIN000025134.

Current Status and Challenges of Endoscopic Treatments for Duodenal Tumors.

BACKGROUND: Superficial tumors of the duodenum, other than ampullary tumors, have been traditionally considered rare. However, reports of this kind of tumor have increased in recent times, and the demand for minimally invasive treatments have also increasing. SUMMARY: Adenomas and intramucosal carcinomas are target lesions for treatment. A preoperative diagnosis has not been established, but unnecessary biopsies increase the difficulty of treatment and should be avoided. Cold snare polypectomy, endoscopic mucosal resection (EMR), and underwater EMR are treatment options for small lesions. Endoscopic submucosal dissection enables secure resection even for large lesions, but it is technically demanding and associated with a higher complication rate. After endoscopic resections, exposure of digestive juices is believed to cause delayed complications. To prevent these complications, several closing and covering methods are proposed, with favorable clinical results. Key message: A treatment method should be chosen based on each patient's situation. With any of the treatment methods, post-resection measures are required to prevent delayed complications. Secure closure of resection wounds seems promising.

Treatment Results of Endoscopic Mucosal Resection with a Ligation Device for Duodenal Neuroendocrine Tumors.

Objective The vertical margin of neuroendocrine tumors (NETs) removed by endoscopic mucosal resection (EMR) is often tumor-positive. We examine the treatment results of endoscopic mucosal resection with a ligation device (EMR-L) for the removal of duodenal NETs located in the submucosal layer without metastasis. EMR-L can be performed with less technical skill, and the ligation device reduces the rate of positive vertical margin. Methods Ten consecutive patients with 10 duodenal NETs resected by EMR-L were enrolled. All of the lesions were located in the submucosal layer, were assessed to be free of metastasis, and were confirmed to be NETs pathologically by an endoscopic biopsy. The endoscopic results, pathological results, and prognosis were all examined. Results The en bloc resection rate and endoscopic complete resection rate were both 100%. Complete resection was achieved pathologically in 7 lesions (70.0%). The vertical margins were negative in all cases. Lymphatic vessel invasion was observed in three patients, all of whom underwent additional surgery with lymph node dissection (one of them also exhibited blood vessel invasion and a positive horizontal margin). No evidence of residual tumors or lymph node metastasis was observed in any of the patients. No recurrence was observed in any of the 10 patients (mean follow-up period: 18.6 months). One patient (10.0%) experienced intraoperative bleeding. Perforation occurred in 1 patient (10.0%), but the condition was managed well by conservative therapy. Conclusion EMR-L was an acceptable method for endoscopically resecting submucosal duodenal NETs, and the NETs resected by EMR-L were tumor-negative in the vertical margins.

Clinical impact of closure of the mucosal defect after duodenal endoscopic submucosal dissection.

BACKGROUND AND AIMS: Delayed adverse events (bleeding or perforation) are major concerns associated with duodenal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of prophylactic closure of the mucosal defect after duodenal ESD. METHODS: This is a retrospective study from a university hospital. One hundred sixty-eight patients (173 lesions) who underwent duodenal ESD between July 2010 and June 2017 were included in this study. The study participants were divided into 3 subgroups according to the degree of closure: complete group, incomplete group, and unclosed group. The proportion of delayed adverse events, maximum serum level of C-reactive protein (CRP), and total length of hospital stay were compared among these subgroups. Moreover, a multivariate logistic regression model was constructed to identify the risk factors for delayed adverse events. RESULTS: The proportion of delayed adverse events in the complete group, incomplete group, and unclosed group were 1.7%, 25%, and 15.6%, respectively. The difference between the complete group and the other groups was significant (P < .01). The maximum serum CRP level was much lower (1.51 ± 2.18 mg/dL vs 6.28 ± 10.0 mg/dL, P < .01), and the length of hospital stay was significantly shorter in the complete group than in the incomplete/unclosed group (median [range] 5 [5-14] days vs 8 [4-59] days, P < .01). Multivariate analysis revealed that complete closure had a significant decrease in delayed adverse events (odds ratio [OR], 0.055; 95% confidence interval [CI], 0.01-0.29; P < .01), and a lesion located distal from the descending part showed a statistical tendency to an increase in delayed adverse events (OR, 4.48; 95% CI, 0.85-23.6; P = .08). CONCLUSION: The present study revealed that complete closure of the mucosal defect after duodenal ESD significantly decreased the number of delayed adverse events and improved other outcomes.

Outcomes of endoscopic resection for superficial duodenal epithelial neoplasia.

BACKGROUND AND AIMS: Pancreaticoduodenectomy is an invasive procedure, and endoscopic resection (ER) is an alternative therapy. However, details regarding the outcomes of ER are unknown, especially for superficial duodenal epithelial neoplasia (SDET). The aim of this study was to elucidate the outcomes of ER for SDET and to compare EMR with endoscopic submucosal dissection (ESD). METHODS: This was a retrospective observational study. From June 2010 to June 2017, 320 cases of endoscopically resected SDET (146 EMR-treated cases and 174 ESD-treated cases) were included in this study. We analyzed the proportions of en bloc resection, R0 resection, perforation, and bleeding as outcomes of ER and compared outcomes between the EMR and ESD groups. Next, we collected data on the features and clinical course of cases with adverse events. RESULTS: The proportions of en bloc resection and R0 resection among all cases were 96.6% and 83.4%, respectively. In over 95% of cases, ESD achieved en bloc resection, regardless of lesion size. The incidences of perforation and bleeding were 8.8% and 3.4%, respectively, and the former was largely successfully managed by conservative treatment. The mortality rate was 0%, and all patients were discharged with a median hospital stay of 8.5 days (range, 4-52 days). Evaluation of the hospital stay duration according to lesion circumference revealed a significantly longer duration for lesions present on the medial wall than for other lesions (median 41 vs 7 days, P = .0331). CONCLUSION: The present study revealed that ER achieved secure en bloc resection, with the treatment type (ESD or EMR) selected according to the lesion size. A lesion located on the medial wall was associated with worse outcomes, such as prolonged hospital stay after perforation.

A Gastric Follicular Lymphoma Presenting as a Submucosal Tumor with a Diagnosis Determined by Endoscopic Resection.

We herein report the case of 74-year-old man with gastric follicular lymphoma resected by endoscopic submucosal dissection (ESD). A submucosal tumor 7 mm in diameter was detected at the gastric middle body. Endoscopic ultrasonography showed a homogenous hypoechoic tumor localized in the submucosa. The tumor was removed by ESD immediately, before further tumor growth would preclude endoscopic resection. The pathological findings indicated follicular lymphoma (FL) with negative horizontal and vertical margins. The clinical stage of FL was confirmed to be stage I by extensive work-up procedures, including contrast-enhanced computed tomography, fluorodeoxyglucose-positron emission tomography, esophagogastroduodenoscopy, and colonoscopy. The patient remains in complete remission without any treatment.

Potential for peritoneal cancer cell seeding in endoscopic full-thickness resection for early gastric cancer.

BACKGROUND AND AIMS: During endoscopic full-thickness resection (EFTR) for cancers, whether exposure of the lumen to the abdominal cavity during the procedure is acceptable is controversial because of the potential risk of tumor cell seeding. To assess the possibility of transplantation as a result of contact with tumor cells during the procedure, we prospectively investigated the ability of cancer cells to be detached by touching the tumor surface. METHODS: In 48 patients with a single early gastric cancer resected by endoscopic submucosal dissection, stamp cytology was performed by touching the surface of the specimens to glass slides. Samples were obtained from cancerous and noncancerous areas, constituting the study and control groups, respectively. The detection rate of malignant class IV or V (C-IV/C-V) samples was investigated with Papanicolaou staining. The rate of CD44v9-positive cases, a cancer stem cell marker, was assessed in C-IV/C-V samples with immunohistochemical staining. RESULTS: Detection rates of C-IV/C-V samples in the cancerous group (53/192 slides, 27.6%) differed significantly from those of the C-IV/C-V samples in the noncancerous group (0/96 slides, 0%). Among the 53 slides of C-IV/C-V samples in the cancerous group, CD44v9 cells were expressed in 18 slides (34.0%). CONCLUSIONS: These data suggest that cancer cells, including cancer stem cells, in early gastric cancers are easily detached via contact with the tumor surface. In EFTR, a nonexposure approach is recommended to avoid the risk of iatrogenic cancer cell seeding via contact with and transplantation of cancer cells.

Rebamipide solution: a novel submucosal injection material to promote healing speed and healing quality of ulcers induced by endoscopic submucosal dissection.

BACKGROUND AND AIMS: Rebamipide is administered perorally to protect the gastric mucosa. We assessed the efficacy and safety of a novel rebamipide solution as a submucosal injection material for endoscopic submucosal dissection (ESD) using an in vivo porcine model. METHODS: An endoscopist blinded to the test agents performed ESDs of hypothetical 30 mm lesions using a 2% rebamipide solution at 2 sites (rebamipide group) and a saline solution at 2 other sites (control group) in the stomachs of 8 pigs. The technical outcomes were compared between the 2 groups. The gastric ulcer stages were evaluated by endoscopy once weekly for 4 weeks after the ESD to determine the healing score (1-6). The pigs were killed at 1 week (n = 2), 2 weeks (n = 2), and 4 weeks (n = 4) after the ESD for pathologic evaluation of ESD-induced ulcers and scarring. RESULTS: There were no significant differences in any of the technical outcomes between the 2 groups, and no adverse events related to the ESD in any of the animals. The healing score was significantly higher in the rebamipide group than in the control group at 2 weeks (P = .027), 3 weeks (P = .034), and 4 weeks (P = .012). In the histopathologic assessment, fibrosis was significantly less extensive in the rebamipide group than in the control group at 2 weeks (P = .02) and 4 weeks (P = .04). CONCLUSIONS: The rebamipide solution appeared to promote both the speed and quality of healing of ESD-induced ulcers by suppressing fibrosis.

Endoscopic string clip suturing method: a prospective pilot study (with video).

BACKGROUND AND AIMS: We developed a suturing method with string and clips for a single-channel endoscope. The feasibility of the string clip suturing method is evaluated in this prospective pilot study. METHODS: This study involved 10 consecutive patients who underwent endoscopic submucosal dissection (ESD) for a duodenal tumor. Polyester string was tied to the arm of a partially out thrust clip. The clip and string can be passed through the instrument channel (3.2 mm) of a single-channel endoscope. The clip with string was placed at the distal edge of the large mucosal defect. A second clip was hooked on the string and placed on the opposite side. Both clips were gathered by pulling the free end of the string, and additional clips were placed to achieve complete closure. This method was compared with that for the previous 10 patients without mucosal closure after duodenal ESD. RESULTS: Mean size of resected specimens was 39.1 ± 12.4 mm. The success rate of the string clip suturing method was 100% (10/10). The mean procedure time was 23.4 ± 13.8 minutes. Perforation during ESD occurred in 1 patient and was successfully closed by this method. None of the treated patients developed serious adverse events after the procedure. Compared with the no-suture group, the length of stay was significantly shorter (P = .038). CONCLUSION: The string clip suturing method appears to be a safe and effective method for closure of large mucosal defects. (Clinical trial registration number: UMIN000023698.).

Effects of EUS-guided intratumoral injection of oligonucleotide STNM01 on tumor growth, histology, and overall survival in patients with unresectable pancreatic cancer.

BACKGROUND AND AIMS: Carbohydrate sulfotransferase 15 (CHST15) promotes tumor growth and invasion and is considered to be an emergent therapeutic target for pancreatic cancer. The aim of this study was to evaluate the safety and efficacy of EUS-guided fine-needle injection (EUS-FNI) of STNM01, the double-stranded RNA oligonucleotide that specifically represses CHST15, for use in patients with pancreatic cancer. METHODS: Six patients with unresectable pancreatic cancer, treated at Tokyo Metropolitan Geriatric Hospital, were used in this open-labeled, investigator-initiated trial. A total of 16 mL STNM01 (250 nM) was injected into the tumor through EUS-FNI. The study's primary endpoint was safety, with a secondary endpoint of tumor response 4 weeks after the initial injection. Some patients received a series of infusions as extensions. The local expression of CHST15 and overall survival (OS) were also evaluated. RESULTS: There were no adverse events. The mean tumor diameter changed from 30.7 to 29.3 mm 4 weeks after injection. Four patients exhibited necrosis of tumor in biopsy specimens. CHST15 was highly expressed at baseline, with 2 patients showing large reductions of CHST15 at week 4. The mean OS of these 2 patients was 15 months, whereas it was 5.7 months for the other 4 patients. CONCLUSIONS: EUS-FNI of STNM01 in pancreatic cancer is safe and feasible. The CHST15 reduction could predict tumor progression and OS. Injections of STNM01 during the beginning of treatment may reduce CHST15 and warrants further investigation.