Lymphovascular invasion (LVI) or pT1b is noncurative after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), and therefore surgery or chemoradiotherapy (CRT) is recommended. However, there has been debate regarding which treatment has better outcomes and whether individual risks should be considered. This was a multicenter, retrospective study conducted at 65 hospitals in Japan. The inclusion criteria were patients with ESCC who underwent ER between January 2006 and December 2015, with pT1a-muscularis mucosa (MM) with LVI or pT1b, with negative vertical margins, cN0M0, and who underwent surgery or CRT. A 1:1 propensity score-matched analysis was performed between two groups. The primary and secondary end points were overall survival (OS) and relapse-free survival (RFS). OS and RFS were also compared between two subgroups: low risk (pT1a-MM with LVI and pT1b without LVI) and high risk (pT1b with LVI) for metastatic recurrence. Among 472 patients, 160 patients were selected from each group. The OS and RFS did not differ between surgery and CRT groups (hazard ratio, 0.887; P = .635 and hazard ratio, 1.036; P = .876, respectively). Subgroup analysis showed that CRT had a better prognosis in the low-risk group, and conversely, surgery had a better prognosis in the high-risk group. But these were not significant. The high-risk CRT group had a significant worse prognosis than the low-risk CRT group. In patients with noncurative ER for ESCC, surgery and CRT showed no difference in long-term outcomes. Indications for CRT in the high-risk group need further investigation because of poor prognosis.

ObjectivesThe risk of postoperative bleeding is high after gastric endoscopic submucosal dissection (ESD) in patients continuously treated with antithrombotic agents (ATAs). The effectiveness of endoscopic hand suturing (EHS) on bleeding after gastric ESD was investigated in patients at high risk of delayed bleeding.MethodsPatients with neoplasms ≤2 cm who underwent gastric ESD and continued to receive perioperative ATAs were enrolled in this multicenter phase II study. The mucosal defect was closed with EHS after removing the lesion. Postoperative bleeding rate was assessed for 3–4 postoperative weeks as a primary outcome measure. The technical success of EHS and adverse events were also assessed. Based on expected and threshold postoperative bleeding rates of 10% and 25%, respectively, we aimed to include 48 patients in the study.ResultsA total of 49 patients were enrolled in the study, and 43 patients were finally registered as the per‐protocol set. The postoperative bleeding rate was 7.0% (3/43 patients; the upper limit of one‐sided 95% confidence interval [CI], 17.1% and 97.5% CI, 19.1%). The upper limits of the CI were below the threshold value (25%), and the postoperative bleeding rate was below the expected value (10%). The technical EHS success rate, closure maintenance rate on postoperative day 3, and postoperative subclinical bleeding rate were 100%, 83%, and 2%, respectively. No severe adverse events related to EHS were observed.ConclusionsEndoscopic hand suturing may prevent postoperative bleeding in patients undergoing gastric ESD while being treated continuously with ATAs (UMIN000038140).

Background We previously developed a Japan Esophageal Society Barrett’s Esophagus (JES-BE) magnifying endoscopic classification for superficial BE-related neoplasms (BERN) and validated it in a nationwide multicenter study that followed a diagnostic flow chart based on mucosal and vascular patterns (MP, VP) with nine diagnostic criteria. Our present post hoc analysis aims to further simplify the diagnostic criteria for superficial BERN. Methods We used data from our previous study, including 10 reviewers’ assessments for 156 images of high-magnifying narrow-band imaging (HM-NBI) (67 dysplastic and 89 non-dysplastic histology). We statistically analyzed the diagnostic performance of each diagnostic criterion of MP (form, size, arrangement, density, and white zone), VP (form, caliber change, location, and greenish thick vessels [GTV]), and all their combinations to achieve a simpler diagnostic algorithm to detect superficial BERN. Results Diagnostic accuracy values based on the MP of each single criterion or combined criteria showed a marked trend of being higher than those based on VP. In reviewers’ assessments of visible MPs, the combination of irregularity for form, size, or white zone had the highest diagnostic performance, with a sensitivity of 87% and a specificity of 91% for dysplastic histology; in the assessments of invisible MPs, GTV had the highest diagnostic performance among the VP of each single criterion and all combinations of two or more criteria (sensitivity, 93%; specificity, 92%). Conclusion The present post hoc analysis suggests the feasibility of further simplifying the diagnostic algorithm of the JES-BE classification. Further studies in a practical setting are required to validate these results.

Background Tumor growth pattern correlates with outcomes in patients with esophageal squamous cell carcinoma (ESCC), however, the clinical significance of the tumor growth pattern in pT1a-lamina propria mucosa (LPM) type of ESCC was unclear. This study was conducted to clarify clinicopathological features of tumor growth patterns in pT1a-LPM type ESCC and the relationship between tumor growth patterns and magnifying endoscopic findings. Methods Eighty-seven lesions diagnosed as pT1a-LPM ESCC were included. Clinicopathological findings including tumor growth pattern and narrow band imaging with magnifying endoscopy (NBI-ME) in the LPM area were investigated. Results Eighty-seven lesions were classified as infiltrative growth pattern-a (INF-a): expansive growth ( n = 81), INF-b: intermediate growth ( n = 4) and INF-c: infiltrative growth pattern ( n = 2). Lymphatic invasion was shown in one INF-b and one INF-c lesion. NBI-ME and histopathological images were matched for 30 lesions. The microvascular pattern was classified into types B1 ( n = 23) and B2 ( n = 7) using the JES classification. All 23 type B1 lesions were classified as INF-a without lymphatic invasion. Type B2 lesions were classified as INF-a ( n = 2), INF-b ( n = 4) and INF-c ( n = 1), and lymphatic invasion was present in two lesions (INF-b and INF-c). The rate of lymphatic invasion was significantly higher in type B2 than type B1 ( p = 0.048). Conclusions The tumor growth pattern of pT1a-LPM ESCC was mostly INF-a in type B1 patterns. Type B2 patterns are rarely present in pT1a-LPM ESCC, however lymphatic invasion with INF-b or INF-c was frequently observed. Careful observation before endoscopic resection with NBI-ME is important to identify B2 patterns to predict histopathology.

To obtain information on implementation of ESD in particpating centres of ten experimental ESD Training Workshops in Salzburg [Dig Endosc 2011;23:282 – 89].

INTRODUCTION:Endoscopic suturing of a mucosal defect is expected to prevent postoperative bleeding after endoscopic submucosal dissection (ESD). Endoscopic suturing causes mucosal deformity, which may interfere with endoscopic surveillance thereafter. We retrospectively investigated long-term chronological changes in mucosal suturing by endoscopic suturing.METHODS:Forty-three patients who underwent endoscopic hand suturing (EHS) after gastric ESD at three institutions were enrolled. First, our hypothesis that the suturing sites healed via inflammation, disappearance of mucosal inversion, and flattening was validated. Subsequently, the duration required to reach each healing step was evaluated.RESULTS:A total of 137 follow-up endoscopies were assessed, in which all cases showed the hypothesized chronological course on the suturing sites. The 95th percentiles of the duration when showing the disappearance of the inflammatory change and the inverted change were 63 days and 15.5 months after the procedure, respectively.DISCUSSION/CONCLUSION:The data show that the mucosal deformity induced by EHS disappeared within 16 months. Endoscopic suturing is thus considered to have a negligible effect on endoscopic surveillance following the procedure.

Background and Aims:Adoption of the endoscopic submucosal dissection (ESD) technique for early GI cancer from Japan requires expert-supervised experimental training before unsupervised implementation of clinical ESD. The aim of this study was to evaluate unsupervised implementation of ESD intention-to-treat (ie, any resection planned and started as en bloc ESD). Methods:ESD workshops (in vivo porcine model) lasted 3.3 days, including a 1-day theory seminar, for 177 participants from 135 Western referral centers. A questionnaire was sent to the senior participant of all 135 centers. This cross-sectional questionnaire survey included main outcome measurements such as performance, organ distribution, and severe adverse events of ESD intention-to-treat. Results:Feedback was received from 113 centers (84%): 73 (54%) ESD centers and 40 centers (30%) with zero ESDs. Ten (7%) had published ESDs; no feedback was received from 12 (9%) centers with unknown status. Altogether, 83 centers (61.5%) performed ESDs: 21 (16%) had >150 ESDs (professional category), 33 (24%) had 31 to 150 ESDs (competent category), and 29 (21.5%) had ≤30 ESDs (initial learning category). Most implemented ESD centers (91% [72 of 79]) were analyzed: centers on initial learning (420 ESD) compared with centers with >30 ESDs (5676 ESDs) performed en bloc ESDs in 64% versus 84%, hybrid ESD in 26% versus 11%, and piecemeal EMR in 10% versus 5.2%. The majority of ESDs (66%-68%) performed were in the colorectum, with a low risk overall (30-day mortality, 0.03%; surgical repair, 3.5% vs 1.7%) and satisfactory outcome (oncosurgery, 7.4% vs 5.2%; local recurrence, 1.5% vs 0.3%). Conclusions:Beyond guideline recommendations, unsupervised implementation of ESD was successful in the colorectum with a step-up approach. Western ESD centers must now aim for professional (ie, >80%) curative ESD.

INTRODUCTION:Curative management after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), which invades the muscularis mucosa (pMM-ESCC) or shallow submucosal layer (pSM1-ESCC), has been controversial. METHODS:We identified patients with pMM-ESCC and pSM1-ESCC treated by ER. Outcomes were the predictive factors for regional lymph node and distant recurrence, and survival data were based on the depth of invasion, lymphovascular invasion (LVI), and additional treatment immediately after ER. RESULTS:A total of 992 patients with pMM-ESCC (n = 749) and pSM1-ESCC (n = 243) were registered. According to the multivariate Cox proportional hazards analysis, pSM1-ESCC (hazard ratio = 1.88, 95% confidence interval 1.15-3.07, P = 0.012) and LVI (hazard ratio = 6.92, 95% confidence interval 4.09-11.7, P < 0.0001) were associated with a risk of regional lymph node and distant recurrence. In the median follow-up period of 58.6 months (range 1-233), among patients with risk factors (pMM-ESCC with LVI or pSM1-ESCC), the 5-year overall survival rates, relapse-free survival rates, and cause-specific survival rates of patients with additional treatment were significantly better than those of patients without additional treatment; 85.4% vs 61.5% ( P < 0.0001), 80.5% vs 53.3% ( P < 0.0001), and 98.5% vs 93.1% ( P = 0.004), respectively. There was no difference in survival rate between the chemoradiotherapy and surgery groups. DISCUSSION:pSM1 and LVI were risk factors for metastasis after ER for ESCC. To improve the survival, additional treatment immediately after ER, such as chemoradiotherapy or surgery, is effective in patients with these risk factors.

Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett’s esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society—Barrett’s esophagus working group (JES-BE) for superficial Barrett’s esophagus-related neoplasms. The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician’s experience level.

Abstract Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real‐world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1–75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2–357). Adverse events occurred in 12.7%. Life‐threatening complications occurred in 0.5%, but there were no treatment‐related deaths. During a median follow‐up period of 46.1 months (range 1–113), the 3‐year overall survival rate, relapse‐free survival rate, cause‐specific survival rate, and larynx‐preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.

This randomized study was designed to evaluate the clinical effect of an elemental diet during chemotherapy in patients with esophageal cancer. The inclusion criteria were as follows: (1) esophageal squamous cell carcinoma, (2) stage IB-IV, (3) schedule to receive docetaxel, cisplatin, and 5-fluorouracil (DCF chemotherapy), (4) 20–80 years old, (5) performance status of 0–2, (6) oral intake ability, and (7) written informed consent. Patients were divided into two groups: the elemental supplementary group and the non-supplementary group. Patients received ELENTAL® (160 g/day) orally 9 weeks after the start of chemotherapy. Primary endpoint was the incidence of grade 2 or higher gastrointestinal toxicity according to the Common Terminology Criteria for Adverse Events, version 4.0. Secondary endpoints were the incidence of all adverse events and the evaluation of nutritional status. Thirty-six patients in the elemental supplementary group and 35 patients in the non-supplementary group were included in the analysis. The incidence of grade 2 or higher gastrointestinal toxicity and all grade 3 or 4 adverse events did not differ significantly between the groups. In the elemental supplementary group, the body weight (p = 0.057), muscle mass (p = 0.056), and blood levels of transferrin (p = 0.009), total amino acids (p = 0.019), and essential amino acids (p = 0.006) tended to be maintained after chemotherapy. Nutritional support provided by an amino acid-rich elemental diet was ineffective for reducing the incidence of adverse events caused by DCF chemotherapy in patients with esophageal cancer.

Background The accurate differentiation between T1a and T1b Barrett's-related cancer has both therapeutic and prognostic implications but is challenging even for experienced physicians. We trained an artificial intelligence (AI) system on the basis of deep artificial neural networks (deep learning) to differentiate between T1a and T1b Barrett's cancer on white-light images. Methods Endoscopic images from three tertiary care centers in Germany were collected retrospectively. A deep learning system was trained and tested using the principles of cross validation. A total of 230 white-light endoscopic images (108 T1a and 122 T1b) were evaluated using the AI system. For comparison, the images were also classified by experts specialized in endoscopic diagnosis and treatment of Barrett's cancer. Results The sensitivity, specificity, F1 score, and accuracy of the AI system in the differentiation between T1a and T1b cancer lesions was 0.77, 0.64, 0.74, and 0.71, respectively. There was no statistically significant difference between the performance of the AI system and that of experts, who showed sensitivity, specificity, F1, and accuracy of 0.63, 0.78, 0.67, and 0.70, respectively. Conclusion This pilot study demonstrates the first multicenter application of an AI-based system in the prediction of submucosal invasion in endoscopic images of Barrett's cancer. AI scored equally to international experts in the field, but more work is necessary to improve the system and apply it to video sequences and real-life settings. Nevertheless, the correct prediction of submucosal invasion in Barrett's cancer remains challenging for both experts and AI.

Objective The aim of the present study was to evaluate the effectiveness and limitations of a serum screening system for predicting the risk of gastric cancer. Methods Serum pepsinogen I (PG I)/pepsinogen II (PG II) and Helicobacter pylori (HP) antibody levels were measured. Subjects were classified into four groupsaccording to their serological status (the ABC classification system). The grade of atrophic gastritis was assessed endoscopically. We evaluated gastric cancer detection rates according to the ABC classification system and the endoscopic grade of atrophy. Patients Individuals who underwent esophagogastroduodenoscopy (EGD) in a health check were prospectively enrolled in the present study. Results According to the ABC classification system, the gastric cancer detection rates in groups A, B, C, and D were 0.07% (4/6,105), 0.5% (8/1,739), 0.8% (16/2,010), and 1.1% (3/281), respectively. The gastric cancer detection rates in subjects with no atrophy, closed type (C-type) atrophy, and open type (O-type) atrophy were 0% (0/4,567), 0.2% (4/2,581), and 0.9% (27/2,987), respectively. In group A (HP(-)/PG(-)), the proportions of subjects with no atrophy, C-type atrophy, and O-type atrophy were 71.2%, 22.8%, and 6.0%, respectively. In group A, the gastric cancer detection rates in subjects with no atrophy, C-type atrophy, and O-type atrophy were 0%, 0.07%, and 0.8%, respectively. Conclusion The ABC classification system is useful for predicting the risk of gastric cancer. However, this system was limited in group A, which included individuals with a high risk of developing gastric cancer. An endoscopic diagnosis of atrophy may be more effective than the ABC classification system for predicting the risk of gastric cancer.

There are few reports on the technical difficulty of gastric endoscopic submucosal dissection (ESD). The aim of this study was to investigate the factors associated with the technical difficulty of ESD for early gastric cancer (EGC) using the data from the multicenter non-randomized confirmatory trial of expanded indication criteria of ESD (JCOG0607). The major inclusion criteria were as follows: (1) histologically proven intestinal-type adenocarcinoma; (2) cT1aN0M0; (3) lesion without finding of ulcer (UL-negative) with > 2 cm in size, or UL-positive with ≤ 3 cm; (4) age 20–75 years. The difficult case was defined as ESD taking ≥ 120 min, piecemeal resection, and/or developing perforation during procedure. Between June 2007 and October 2010, 470 patients were enrolled from 29 institutions. Median procedure time was 79 (range 14–462) min, and it was ≥ 120 min in 127 patients. Twelve patients developed perforation during ESD, and the procedure time was ≥ 120 min in 9 of them. Therefore, 130 patients (27.7%) were identified as difficult cases. Multivariable analysis showed that UL-negative with > 5 cm (vs. UL-negative with ≤ 3 cm, odds ratio, 24.993; 95% CI 6.130–101.897, p < 0.0001) had the largest odds ratio and followed by UL-negative with 3–5 cm upper or middle portion of stomach and age ≤ 60 years were significantly associated with difficulty. UL-negative lesion with > 3 cm, upper or middle portion of stomach and age ≤ 60 years were independent factors associated with technical difficulty of ESD for EGC. Trial registered number was UMIN000000737.

We describe the case of a 70-year-old man with diabetic nephropathy undergoing hemodialysis. Four years following hemodialysis, he started taking lanthanum carbonate 1500 mg/day and lansoprazole 30 mg/day. Nine years following hemodialysis, he underwent screening esophagogastroduodenoscopy, which demonstrated the presence of the whitish cobblestone-like mucosa in the gastric corpus and multiple reddish depressed lesions with annular whitish mucosa in the antrum. With magnified narrow-band imaging endoscopy, a yellowish–white substance was observed in the villous structure, and subepithelial vessels were observed on the yellowish–white substance. Biopsies were taken from the whitish cobblestone-like mucosa of the upper corpus, a reddish depressed part of the antrum. Histologically, aggregates of cells containing amphophilic fine granular material were found in the mucosal interstitium. These cells stained positive for CD68 and were identified as histiocytes. Since he had been taking lanthanum carbonate for 5 years, we considered the possibility of histiocyte-mediated phagocytosis of lanthanum. Digital mapping via scanning electron microscopy with energy-dispersive X-ray spectrometry showed the presence of lanthanum and phosphorus in the interstitium and cytoplasm of histiocytes. The white, rough mucosa in the gastric body appeared 6 months following the commencement of lanthanum administration and still exists 3 years and 5 months after discontinuation of lanthanum.

Compared with other endoscopic treatments, gastric endoscopic submucosal dissection (ESD) has a relatively high risk of adverse events. Postoperative bleeding is a particularly urgent issue to address, especially as the number of patients taking antithrombotic agents (ATAs) for other disorders is increasing. Endoscopic hand-suturing (EHS), which involves continuous linear suturing endoscopically by using a commercially available absorbable barbed suture and a prototype of a through-the-scope flexible needle holder, provides secure intraluminal mucosal closure and should decrease the risk of adverse events after gastric ESD.

Background and Aims: Endoscopic hand-suturing (EHS) provides secure intraluminal mucosal closure and should decrease the risk of adverse events after gastric endoscopic submucosal dissection (ESD). We prospectively investigated the feasibility and safety of EHS after gastric ESD, particularly for preventing post-ESD bleeding. Methods: Patients scheduled for gastric ESD at 3 institutions were prospectively recruited. Just after ESD, the mucosal defect was closed by EHS. The primary outcome was endoscopic assessment of adequately sustained closure of the defect on postoperative day 3. Endoscopy was performed to assess maintenance of the closure for the primary outcome. During postoperative weeks 3 to 4, patients were interviewed as outpatients about any occurrence of delayed bleeding. Results: Data from 30 patients (15 each who did or did not take antithrombotic agents) were analyzed. Mucosal closure by EHS was completed in 29 of 30 cases (97%) and was well maintained on postoperative day 3 in 25 cases (84%). Emergency endoscopy was required for major postoperative bleeding in 3 cases (10%), including 1 in which suturing had been incomplete. Excluding 1 patient with a remnant stomach, the other 24 with sustained closure had no bleeding, regardless of whether they did or did not take antithrombotic agents (0/11 and 0/13, respectively). No serious adverse events occurred during EHS. Conclusions: Results show that EHS is feasible and safe with favorable outcomes. Provided that mucosal suturing is successfully completed and sustained, post-ESD bleeding can be decreased even in patients undergoing antithrombotic therapy.

Background: Additional surgery is recommended after noncurative endoscopic submucosal dissection (ESD) for early gastric cancer due to the risk of lymph node metastasis. However, age may affect the clinical management of these patients. Objectives: The aim of our retrospective multicenter study was to clarify whether age affects decision-making after noncurative ESD and if the decision affects long-term outcomes. Methods: Age was classified as follows: non-elderly, <70 years (n = 811); elderly, 70–79 years (n= 760); and super-elderly, ≥80 years (n = 398). Age associations with the selection for additional surgery were evaluated using logistic regression analysis. Long-term outcomes were also evaluated in each age group. Results: Age was inversely related to the rate of additional surgery, which ranged from 70.0% in the non-elderly group to 20.1% in the super-elderly group (p < 0.001). On multivariate analysis, age <70 years (versus age ≥80 years) was associated with the ­selection of additional surgery (OR 18.6). Overall survival (OS) in patients who underwent additional surgery was ­significantly higher in the non-elderly and elderly groups (p< 0.001), whereas the difference was not significant in the super-elderly group (p = 0.23). Conclusions: Despite the fact that almost 80% of super-elderly patients did not undergo additional surgery, the difference of OS between patients with and without additional surgery was not significant only in patients ≥80 years. Therefore, establishment of criteria for selecting treatment methods after noncurative ESD in elderly patients is required.