Narrow band imaging under less-air condition improves the visibility of superficial esophageal squamous cell carcinoma.

BACKGROUND: The current virtual chromoendoscopy equipment cannot completely detect superficial squamous cell carcinoma (SCC) in the esophagus, despite its development in the recent years. Thus, in this study, we aimed to elucidate the appropriate air volume during endoscopic observation to improve the visibility of esophageal SCC. METHODS: This retrospective study included a total of 101 flat type esophageal SCCs identified between April 2017 and January 2019 at the Department of Gastrointestinal Oncology, Osaka International Cancer Institute. Video images of narrow band imaging (NBI) under both less-air and standard-air conditions were recorded digitally. Videos were evaluated by five endoscopists. Relative visibility between less-air and standard-air conditions of the brownish area, brownish color change of the epithelium, and dilated intrapapillary capillary loop (IPCL) were graded as 5 (definitely better under less-air condition) to 1 (definitely worse under less-air condition), with 3 indicating average visibility (equivalent to standard-air observation). RESULTS: The mean (standard deviation) visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs under less-air condition were 3.94 (0.58), 3.73 (0.57), and 4.13 (0.60), respectively, which were significantly better than that under standard-air condition (p < 0.0001). Esophageal SCC evaluated as ≥ 4 in the mean visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs accounted for 50% (51/101 lesions), 34% (34/101 lesions), and 67% (68/101 lesions), respectively. CONCLUSIONS: The present results suggested that NBI with less air might improve the visibility of flat type esophageal SCC compared with NBI with standard air. Less-air NBI observation may facilitate the detection of flat type esophageal SCC. TRIAL REGISTRATION: The present study is a non-intervention trial.

Differentiation between duodenal neoplasms and non-neoplasms using magnifying narrow-band imaging - Do we still need biopsies for duodenal lesions?

OBJECTIVES: Endoscopic biopsies for nonampullary duodenal epithelial neoplasms (NADENs) can induce submucosal fibrosis, making endoscopic resection difficult. However, no biopsy-free method exists to distinguish between NADENs and non-neoplasms. We developed a diagnostic algorithm for duodenal neoplasms based on magnifying endoscopy findings and evaluated the model's diagnostic ability. METHODS: Magnified endoscopic images and duodenal lesion histology were collected consecutively between January 2015 and April 2016. Diagnosticians classified the surface patterns as pit, groove or absent. In cases of nonvisible surface patterns, the vascular pattern was evaluated to determine regularity or irregularity. The correlation between our algorithm (pit-type or absent with irregular vascular pattern) and the lesion histology were evaluated. Four evaluators, who were blinded to the histology, also classified the endoscopic findings and evaluated the diagnostic performance and interobserver agreement. RESULTS: Endoscopic images of 114 lesions were evaluated (70 NADENs and 44 non-neoplasms, 31 in the superior and 83 in the descending and horizontal duodenum). Of the NADEN surface patterns, 88% (62/70) were pit-type, while 79% (35/44) of the non-neoplasm surface patterns were groove-type. Our diagnostic algorithm for differentiating NADENs from non-neoplasms was high (sensitivity 96%, specificity 95%) in the descending and horizontal duodenum. The evaluators' diagnostic performances were also high, and interobserver agreement for the algorithm was good between each diagnostician and evaluator (κ = 0.60-0.76). CONCLUSION: Diagnostic performance of our algorithm sufficiently enabled eliminating endoscopic biopsies for diagnosing the descending and horizontal duodenum.

Endoscopic appearance of esophageal xanthoma.

Background and study aims Esophageal xanthomas are considered to be rare, and their endoscopic diagnosis has not been fully elucidated. The aim of the present study was to determine the characteristics of the endoscopic appearance of esophageal xanthomas. Patients and methods This was a retrospective study of consecutive patients with histologically diagnosed esophageal xanthomas at a referral cancer center in Japan. The endoscopic appearance, by magnifying or image-enhanced endoscopy, and histological findings of esophageal xanthomas were investigated. Results Seven patients (six men and one woman) were enrolled. All of the patients had a solitary lesion, and the median size was 2 mm (range, 1 - 5 mm). Conventional white-light endoscopy showed the lesions as flat areas with yellowish spots in four cases and slightly elevated yellowish lesions in three cases. Magnifying endoscopy, performed in six patients, revealed the lesions as areas with aggregated minute yellowish spots with tortuous microvessels inside. Magnifying narrow-band imaging contrasted the yellowish spots and microvessels better than white-light endoscopy. In all lesions, histological examination showed that the yellowish spots corresponded to papillae filled with foam cells. The foam cells were strongly immunopositive for CD68, and in all lesions, CD34-positive intrapapillary capillaries surrounded the aggregated foam cells. The different morphologies of the flat and slightly elevated lesions corresponded to different densities of papillae filled with foam cells. Conclusions Magnifying endoscopy revealed minute yellowish spots with tortuous microvessels inside. These correspond well with histological findings and so may be useful in the diagnosis of esophageal xanthomas.

Efficacy of vonoprazan in prevention of bleeding from endoscopic submucosal dissection-induced gastric ulcers: a prospective randomized phase II study.

BACKGROUND: Vonoprazan, potassium-competitive acid blocker, is expected to reduce incidence of delayed bleeding after gastric endoscopic submucosal dissection (ESD); however, preliminary data to design a large-scale comparative study are lacking. This study aimed to assess the efficacy of vonoprazan in preventing delayed bleeding after gastric ESD. METHODS: In this single-center randomized phase II trial, a modified screened selection design was used with a threshold non-bleeding rate of 89% and an expected rate of 97%. In this design, Simon's optimal two-stage design was first applied for each parallel group, and efficacy was evaluated in comparison with the threshold rate using binomial testing. Patients were randomly assigned in a 1:1 ratio to receive either vonoprazan 20 mg (VPZ group) or lansoprazole 30 mg (PPI group) for 8 weeks from the day before gastric ESD. The primary endpoint was the incidence of delayed bleeding, defined as endoscopically confirmed bleeding accompanied by hematemesis, melena, or a decrease in hemoglobin of ≥ 2 g/dl. RESULTS: Delayed bleeding occurred in three of 69 patients (4.3%, 95% CI 0.9-12.2%, p = 0.047) in the VPZ group, and four of 70 (5.7%, 95% CI 1.6-14.0%, p = 0.104) in the PPI group. As only vonoprazan showed significant reduction in delayed bleeding compared with the threshold rate, it was determined to be efficacious treatment. CONCLUSIONS: Vonoprazan efficaciously reduced the delayed bleeding rate in patients with an ESD-induced gastric ulcer. A large-scale, randomized, phase III study is warranted to definitively test the effectiveness of vonoprazan compared with proton pump inhibitors.

Impact of electrosurgical unit mode on post esophageal endoscopic submucosal dissection stricture in an in vivo porcine model.

BACKGROUND AND AIM: Strictures are a major complication of esophageal endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma. Post ESD, stricture develops during the process of scar formation, which is related to inflammation caused by ESD. We planned a study to evaluate whether certain electrosurgical unit modes could attenuate strictures after esophageal ESD. METHODS: A total of 16 ESD, three-quarters of the esophageal circumference, were performed in four live pigs. A ball-tip Flush knife was used for mucosal incision. Submucosal dissection was performed using a Hook knife in monopolar mode and a ball-tip Jet B-knife in bipolar mode. Applied electrosurgical unit modes were FORCED COAG, SWIFT COAG, SPRAY COAG, ENDO CUT in monopolar mode, and FORCED COAG in bipolar mode. One month after ESD, the pigs were killed humanely and the severity of strictures and fibrosis was assessed. RESULTS: The resected site in the esophagus showed complete mucosal regrowth and scar formation in all pigs. The quotients of stricture following ENDO CUT, SWIFT COAG, FORCED COAG effect2, FORCED COAG effect3, FORCED COAG effect4, SPRAY COAG, and Bipolar FORCED COAG mode were 16 %, 28 %, 38 %, 33 %, 51 %, 39 %, and 47 %, respectively. The equivalent quotients of fibrosis were 7 %, 28 %, 31 %, 30 %, 35 %, 63 %, and 100 %, respectively. ENDO CUT mode was associated with the lowest mean quotients of stricture and fibrosis. CONCLUSION: ENDO CUT mode showed promising results to attenuate fibrosis and strictures after esophageal ESD.

Line-assisted complete closure for a large mucosal defect after colorectal endoscopic submucosal dissection decreased post-electrocoagulation syndrome.

BACKGROUND AND AIM: The incidence of post-endoscopic submucosal dissection (ESD) coagulation syndrome (PECS) can be decreased by closing mucosal defects. However, large mucosal defects after colorectal ESD cannot be closed endoscopically. We established line-assisted complete clip closure (LACC), a novel technique for large mucosal defects after colorectal ESD. We evaluated the prophylactic efficacy of LACC for preventing PECS. METHODS: Sixty-one consecutive patients on whom LACC after colorectal ESD was attempted from January 2016 to August 2016 were analyzed. After exclusion of patients with incomplete LACC and adverse events during ESD, 57 patients comprised the LACC group. In contrast, 495 patients who did not undergo closure of a mucosal defect comprised the control group. Propensity score matching was used to adjust for patients' backgrounds. Treatment outcomes were evaluated between the groups. RESULTS: Median resected specimen size in the LACC-attempted group was 35 mm (range, 20-72 mm), and LACC success rate was 95% (58/61). Median procedure time of LACC was 14 min. In the LACC group, incidence of PECS was only 2%, and no delayed bleeding or perforation occurred. Propensity score matching created 51 matched pairs. Adjusted comparisons between the LACC and control groups showed a lower incidence of PECS (0% vs 12%, respectively; P = 0.03) and shorter hospitalization (5 vs 6 days, respectively; P < 0.001) in the LACC group. CONCLUSION: This study suggests that LACC can effectively reduce the incidence of PECS, although further large-scale studies are warranted.

Efficacy of traction-assisted colorectal endoscopic submucosal dissection using a clip-and-thread technique: A prospective randomized study.

BACKGROUND AND AIM: Colorectal endoscopic submucosal dissection (ESD) remains challenging because of technical difficulties, long procedure time, and high risk of adverse events. To facilitate colorectal ESD, we developed traction-assisted colorectal ESD using a clip and thread (TAC-ESD) and conducted a randomized controlled trial to evaluate its efficacy. METHODS: Patients with superficial colorectal neoplasms (SCN) ≥20 mm were enrolled and randomly assigned to the conventional-ESD group or to the TAC-ESD group. SCN ≤50 mm were treated by two intermediates, and SCN >50 mm were treated by two experts. Primary endpoint was procedure time. Secondary endpoints were TAC-ESD success rate (sustained application of the clip and thread until the end of the procedure), self-completion rate by the intermediates, and adverse events. RESULTS: Altogether, 42 SCN were analyzed in each ESD group (conventional and TAC). Procedure time (median [range]) for the TAC-ESD group was significantly shorter than that for the conventional-ESD group (40 [11-86] min vs 70 [30-180] min, respectively; P < 0.0001). Success rate of TAC-ESD was 95% (40/42). The intermediates' self-completion rate was significantly higher for the TAC-ESD group than for the conventional-ESD group (100% [39/39] vs 90% [36/40], respectively; P = 0.04). Adverse events included one intraoperative perforation in the conventional-ESD group and one delayed perforation in the TAC-ESD group. CONCLUSION: Traction-assisted colorectal endoscopic submucosal dissection reduced the procedure time and increased the self-completion rate by the intermediates (UMIN000018612).

Erratum: Dive to the Underwater World: A Water Immersion Technique for Endoscopic Submucosal Dissection of Gastric Neoplasms.

This corrects the article DOI: 10.1038/ajg.2016.595.

Safety of cold snare polypectomy for duodenal adenomas in familial adenomatous polyposis: a prospective exploratory study.

BACKGROUND: Cold snare polypectomy (CSP) to remove multiple duodenal adenomas (MDAs) in patients with familial adenomatous polyposis (FAP) could be an effective and less invasive method than more extensive surgery. The aim of the present study was to determine the safety of this procedure. METHODS: This prospective exploratory study included 10 consecutive patients with FAP and MDAs who underwent CSP for as many as 50 duodenal adenomas. The primary outcome was the incidence of severe adverse events. RESULTS: 10 patients were enrolled and underwent 332 CSPs from June 2016 to January 2017. The median procedure time was 33 minutes (range 25 - 53), and the median number of polyps removed during a single session was 35 (range 10 - 50). Most of the removed polyps were ≤ 10 mm. None of the 10 patients experienced a severe adverse event. One patient developed arterial bleeding during the procedure, but it was easily managed using hemoclips. CONCLUSIONS: CSP for MDAs in patients with FAP was safe. The long-term efficacy of this procedure should be investigated.

Comparison of ENDO CUT mode and FORCED COAG mode for the formation of stricture after esophageal endoscopic submucosal dissection in an in vivo porcine model.

BACKGROUND AND STUDY AIM: Stricture is a major complication of esophageal endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma. To date, various methods have been developed to prevent stricture. However, the mechanism by which different electrosurgical unit (ESU) modes affect the formation of post-ESD stricture has not been evaluated. This study aimed to compare the degree of stricture caused by two major ESU modes (ENDO CUT mode and FORCED COAG mode) in a porcine model. METHODS: Twelve ESD procedures covering half of the circumference were performed in six pigs. Mucosal incision was performed with a ball-tip flush knife and submucosal dissection was performed with a hook knife; the two modes used were ENDO CUT I (Effect 2, Duration 2, Interval 3) and FORCED COAG mode (Effect 3, 40 W) (VIO300D, ERBE Germany). The pigs were killed humanely 30 days after ESD, and the severity of stricture and fibrosis was assessed. RESULTS: The resected site of the esophagus showed complete mucosal regrowth and scar formation in all pigs. There was no significant difference between the two modes in procedure time and size of resected specimen (14.4 ± 2.4 and 15.9 ± 6.1 min, P = 0.589; 626 ± 148, 661 ± 186 mm2, P = 0.74, respectively). Stricture rate and severity of fibrosis in the submucosal layer were significantly lower in ENDO CUT mode than in FORCED COAG mode (31.5 ± 16.0% vs 44.3 ± 11.6%, P = 0.046; 36.2 ± 17.1% vs 60.4 ± 26.8%, P = 0.024, respectively). CONCLUSIONS: ENDO CUT mode showed promising ability to attenuate fibrosis and stricture after esophageal ESD.

Underwater endoscopic mucosal resection for superficial nonampullary duodenal adenomas.

BACKGROUND AND STUDY AIM: Underwater endoscopic mucosal resection (UEMR) was recently developed in a Western country. A prospective cohort study to investigate the effectiveness of UEMR was conducted in patients with small superficial nonampullary duodenal adenomas. PATIENTS AND METHODS: Patients with duodenal adenomas ≤ 20 mm were enrolled. After the duodenal lumen had been filled with physiological saline, UEMR was performed without submucosal injection. Endoclip closure was attempted for all mucosal defects after UEMR. Follow-up endoscopy with biopsy was performed 3 months later. The primary end point was the complete resection rate, defined as neither endoscopic nor histological residue of adenoma at the follow-up endoscopy. RESULTS: 30 patients with 31 lesions were enrolled. The mean (SD) tumor size was 12.0 mm (7.3). The complete resection rate was 97 % (90 % confidence interval, 87 % - 99 %). The en bloc resection rate was 87 %. All mucosal defects were successfully closed by endoclips. No adverse events occurred except for one case of mild aspiration pneumonia. CONCLUSIONS: UEMR is efficacious for the treatment of small duodenal adenomas, but further large-scale trials are warranted to confirm these results.

Efficacy and Safety of Endoscopic Resection Followed by Chemoradiotherapy for Superficial Esophageal Squamous Cell Carcinoma: A Retrospective Study.

OBJECTIVES: The reported 1- and 3-year overall survival rates after esophagectomy for stage I superficial esophageal squamous cell carcinoma (SESCC) are 95-97% and 86%, and those after definitive chemoradiotherapy (CRT) are 98% and 89%, respectively. This study was performed to elucidate the efficacy and safety of another treatment option for SESCC: endoscopic resection (ER) followed by CRT. METHODS: We retrospectively reviewed the overall survival, recurrence, and grade ≥3 adverse events of consecutive patients who refused esophagectomy and underwent ER followed by CRT for SESCC from 1 January 2006 to 31 December 2012. RESULTS: In total, 66 patients with SESCC underwent ER followed by CRT during the study period, and complete follow-up data were available for all patients. The median age was 67 (range, 45-82) years, and the median observation period was 51 (range, 7-103) months. Local and metastatic recurrences occurred in 2 (3%) and 6 (9%) patients, respectively, and 17 (26%) patients died. The 1-, 3-, and 5-year overall survival rates were 98%, 87%, and 75%, respectively. One of the 23 patients with mucosal cancer and 5 of 43 with submucosal cancer developed metastatic recurrences (P=0.65). Five of the 61 patients with negative vertical resection margin and 1 of 5 with positive vertical resection margin developed metastatic recurrences (P=0.39). None of the 30 patients without lymphovascular involvement developed metastatic recurrences; however, 6 of 36 patients with lymphovascular involvement developed metastatic recurrences (P=0.0098). Grade ≥3 adverse events occurred in 21 (32%) patients and all adverse events were associated with CRT, hematological adverse events in 13 (20%), and non-hematological adverse events in 9 (14%). CONCLUSIONS: ER followed by CRT provides survival comparable with that of esophagectomy or definitive CRT and has a low local recurrence rate. A particularly favorable outcome is expected for cancers without lymphovascular involvement.

Investigation of mucosal pattern of gastric antrum using magnifying narrow-band imaging in patients with chronic atrophic fundic gastritis.

BACKGROUND: Magnifying narrow-band imaging (M-NBI) can reportedly help predict the presence and distribution of atrophy and intestinal metaplasia in the gastric corpus. However, the micro-mucosal pattern of the antrum shown by M-NBI differs from that of the corpus. We studied the distribution and histology of the micro-mucosal pattern in the antrum based on magnifying endoscopy. METHODS: Endoscopic images of the greater curvature of the antrum were evaluated in 50 patients with chronic atrophic fundic gastritis (CAFG). The extent of CAFG was evaluated by autofluorescence imaging. The micro-mucosal pattern was evaluated by M-NBI and classified into groove and white villiform types. The localization of white villiform type mucosa was classified into three types in relation to the areae gastricae: null, central, and segmental types. Biopsies were taken from regions showing different micro-mucosal patterns. Associations among the extent of CAFG, micro-mucosal pattern, and histology were examined. RESULTS: As the extent of CAFG increased, the proportion of white villiform type mucosa increased, whereas that of groove type mucosa decreased (P=0.022). In patients with extensive CAFG, most of the areae gastricae was composed of the segmental or central type of white villiform type mucosa (P=0.044). The white villiform type mucosa had significantly higher grades of atrophy (P=0.002) and intestinal metaplasia (P<0.001) than did the groove type mucosa. CONCLUSION: White villiform type mucosa is indicative of atrophy and intestinal metaplasia in the gastric antrum. It extends to the whole or central part of the areae gastricae as CAFG becomes more extensive.

Technical feasibility of line-assisted complete closure technique for large mucosal defects after colorectal endoscopic submucosal dissection.

Background and study aims Complete closure of large mucosal defects after colorectal endoscopic submucosal dissection (C-ESD) is considered impossible in most cases because of the limited width of the open clip. We therefore invented a simple closure technique using clip-and-line, named "line-assisted complete closure (LACC)", and assessed its technical feasibility. Patients and methods Between January and February 2016, we performed LACC in 11 patients after C-ESD and included them in this retrospective feasibility study. Outcome measures were procedural success rate, procedure time, and post-procedural complications. Results The median size of the resected specimen was 36 mm (range 30 - 72 mm). Procedural success was achieved in 10 of 11 cases (91 %). Those 10 cases required a median of 9 endoclips (range 6 - 12) for complete closure. Median procedure time for LACC was 14 minutes (range 6 - 22). No complications were observed in any of the cases after the procedure. Conclusion LACC is a simple and feasible technique for complete closure of large mucosal defects after C-ESD.

Pethidine hydrochloride is a better sedation method for pharyngeal observation by transoral endoscopy compared with no sedation and midazolam.

BACKGROUND AND AIM: Standard surveillance methods for pharyngeal cancer have not been established. We conducted a randomized controlled trial to investigate the best sedation method for pharyngeal observation using transoral endoscopy. METHODS: In total, 120 patients who underwent surveillance or diagnostic examinations for esophageal cancer were enrolled and divided equally into three groups (no sedation, midazolam, or pethidine hydrochloride). In the midazolam group, midazolam was given i.v. maintaining a Ramsay score of 3. In the pethidine group, pethidine hydrochloride (35 mg) given i.v. Seven sites in five pharyngeal regions were observed on insertion of the endoscope, and graded (0 = poor, 1 = good). After examination, the five pharyngeal regions were scored using a seven-point scale. Primary endpoint was the total score from the five pharyngeal regions. Secondary endpoints were the proportion of the perfect score using the seven-point scale, discomfort score, and adverse events. RESULTS: Mean total scores for the no sedation group, the midazolam group and the pethidine group were 5.7, 5.5, and 6.8, respectively (P < 0.0001). Proportion of patients with a perfect score for the no sedation group, the midazolam group and the pethidine group were 53%, 35%, and 89%, respectively (P < 0.0001). The pethidine group had better results than the other two groups. Discomfort score and adverse events were low in the pethidine group. CONCLUSION: Pethidine hydrochloride is a feasible and safe sedation method, and was superior to no sedation and midazolam regarding pharyngeal observation of esophageal cancer patients.

First reports of esophageal adenocarcinoma with white globe appearance in Japanese and Caucasian patients.

Background and study aims: Better endoscopic diagnosis in case of Barrett's esophagus is still needed. White globe appearance (WGA) is a novel endoscopic marker for gastric adenocarcinoma, with high sensitivity for differentiating between gastric cancer/high-grade dysplasia and other lesions. We report 2 cases of esophageal adenocarcinoma with WGA. In Case 1, esophagogastroduodenoscopy (EGD) revealed a 10-mm esophageal adenocarcinoma in a 48-year-old Japanese woman with short-segment Barrett's esophagus. A small (< 1 mm) white globular lesion, typical of WGA, was observed under the epithelium by magnifying narrow-band imaging. A dilated neoplastic gland with eosinophilic material and necrotic epithelial fragments was identified at the site of the WGA by histologic examination. In Case 2, EGD revealed a 5-mm esophageal adenocarcinoma in a 60-year-old Caucasian man with long-segment Barrett's esophagus. A typical WGA was observed by magnifying narrow-band imaging and similar histologic findings were identified at the site of the WGA. WGA could be a reliable endoscopic finding for target biopsy in esophageal adenocarcinoma, if its specificity is as high as in gastric cancer. The clinical implications of WGA in patients with Barrett's esophagus should be investigated further.

Endoscopic surveillance of head and neck cancer in patients with esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: Multiple squamous cell carcinomas (SCCs) frequently arise in the upper aerodigestive tract, referred to as the field cancerization phenomenon. The aim of this study was to elucidate the detailed clinical features of second primary head and neck (H&N) SCCs arising in patients with esophageal SCC. PATIENTS AND METHODS: A total of 818 patients underwent endoscopic resection for superficial esophageal cancer between January 2006 and December 2013. Of these, 439 patients met our inclusion criteria, and we retrospectively investigated the incidence, primary sites, and stages of second primary H&N SCCs in these patients. RESULTS: A total of 53 metachronous H&N SCCs developed in 40 patients after a median follow-up period of 46 months (range 9 - 109). The cumulative incidence rates of metachronous H&N SCCs at 3, 5, and 7 years were 5.3 %, 9.7 %, and 17.2 %, respectively. These lesions were frequently located at pyriform sinus or in the posterior wall of the pharynx (70 %, 37/53 lesions). Most of the lesions were detected at an early stage, though 4 lesions were associated with lymph node metastasis when their primary sites were detected (1 postcricoid area, 2 posterior wall of hypopharynx, and 1 lateral wall of oropharynx). CONCLUSIONS: Patients with esophageal SCC should undergo careful inspection of the pyriform sinus and posterior wall of the pharynx for detection of H&N SCCs. Methods to open the hypopharyngeal space, such as the Valsalva maneuver, should be included in the surveillance program.