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4029 Background: The incidence of lymph node metastasis (LNM) in pathological T1b (pT1b) gastric cancer (GC) is around 20% and the majority of them have no LNM. The Cancer Genome Atlas Research Network proposed the concept of molecular phenotype classifying GC into 4 phenotypes including Epstein-Barr virus-CIMP (EBV). EBV positive gastric cancer (EBVGC) is associated with a low prevalence of LNM; however, EBV status is not considered in the present indication of endoscopic resection (ER). We aimed to clarify the implication of EBV status for ER of pT1b GC. Methods: Consecutive cases of pT1b GCs treated with curative surgery between 2005 and 2014 were retrospectively analyzed. Tissue microarray was made and EBV-encoded RNA in situ hybridization was performed for evaluation of EBV status. Clinicopathological factors and LNM status were compared between EBVGC and non-EBVGC groups. Results: Among the 1221 pT1b GCs that underwent gastrectomy with regional lymph node dissection, 898 pT1bGCs were eligible in this study. EBVGC accounted for 7.9% (71 of 898) cases. Compared to non-EBVGC, EBVGC was more frequent in males (p = 0.0055), the upper third region (p < 0.0001), showed elevated growth features (p = 0.0059), and was associated with a lower frequency of accompanying ulceration (p = 0.002), greater depth of submucosal invasion (p = 0.017), and lower frequency of lymphatic invasion (p < 0.0001). Frequency of LNM was significantly lower in EBVGC than in non-EBVGC (4.2% vs. 21.9%, p < 0.0001). In EBVGC, tumors without lymphovascular invasion showed significantly lower frequency of LNM than those with lymphovascular invasion (0 of 50, 0%; vs 3 of 21, 14.3%; p = 0.023). Histologically, 84.5% (60 of 71) of EBVGC included carcinomas with lymphoid stroma and/or lace pattern components. Conclusions: pT1b EBVGC is a convincing candidate for ER, regardless of risk factors other than lymphovascular invasion.

Background and Aim Type I gastric carcinoids (TIGC) are associated with chronic atrophic gastritis (CAG) with hypergastrinemia and hyperplasia of enterochromaffin-like cells. Several treatment options are currently available for these tumors including total gastrectomy, partial resection, antrectomy, endoscopic resection and endoscopic surveillance. The present study evaluated different treatment approaches and clinical outcomes of patients with TIGC in Japan. Methods Between 1991 and 2011, 82 patients with TIGC were identified at multicenter institutions in Japan. Patient demographics, tumor size, depth of invasion, vessel involvement, treatment approach, Helicobacter pylori infection, serum gastrin level, recurrence-free survival (RFS) and disease-specific survival (DSS) were analyzed. Results Median age of all patients at the time of diagnosis was 56 years (range, 24−79 years). There were 44 males and 38females. Patients underwent endoscopic surveillance (n = 25), endoscopic resection (n = 41) or surgical resection (n = 16). Intramucosal invasion was found in 19 patients, submucosal invasion in 44 patients and muscularis propria invasion in one patient. Tumor diameter was ≤10 mm in 71 patients, 11–20 mm in five patients and ≥21 mm in five patients. None of the patients showed rapidly growing tumors, local recurrence or metastasis. The median (range) follow-up period was 7 (0–20) years. RFS was 97.6% and DSS was 100% in all the patients. Conclusion The prognosis of TIGC patients treated by different modalities in Japan is favorable regardless of the generational change of management for TIGC.

The topical antispasmodic agent l-menthol is useful for inhibiting gastric peristalsis during diagnostic upper gastrointestinal endoscopy. However, it remains unclear whether l-menthol is similarly effective during therapeutic endoscopy, thereby improving treatment outcomes in a clinical setting.A total of 83 patients scheduled to undergo endoscopic treatment at 8 Japanese referral centers were randomly assigned to receive l-menthol or placebo. The degree of gastric peristalsis (peristaltic score: grade 1-5) was assessed by an independent committee. The primary outcome was the proportion of subjects in whom no or mild peristalsis (grade 1 or 2) was maintained throughout endoscopic treatment. Secondary outcomes were the duration of sustained response and the incidence of adverse drug reactions.The proportion of patients with no or mild peristalsis was significantly higher in the l-menthol group (85.4 %, 95 % confidence intervals 70.8-94.4: 35/41 subjects) than in the placebo group (39.0 %, 24.2-55: 16/41; P0.001). The sustained response rates in the l-menthol and the placebo were, respectively, 90.0 and 39.6 % 30 min post-dose, and 79.9 and 35.7 % at the completion of the resection. The sustained response rates were significantly higher in the l-menthol group than in the placebo group (P0.001, log-rank test). The incidence of adverse drug reactions did not differ significantly between the two groups (P = 1.000).During gastric endoscopic submucosal dissection, spraying l-menthol on the gastric mucosa significantly suppressed peristalsis, with minimal adverse drug reactions as compared with placebo. l-menthol solution might be useful for therapeutic endoscopy.

It has been described that most cases of Barrett's esophageal adenocarcinoma in Japan are cases of Barrett's esophageal adenocarcinoma on a background of short-segment Barrett's esophagus, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the esophagogastric junction. Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction, so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone. We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as annular vascular formations (AVF) by magnifying endoscopy with narrow-band imaging (ME-NBI), and have verified it by 3-D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontal cross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 μm from the surface and disappeared at a depth of approximately 300 μm. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 μm underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected.

A 67-year-old man, presenting with anemia and suspected gastric cancer, was referred to our hospital, where he underwent esophagogastroduodenoscopy (EGD). Biopsy revealed densely populated semi-circular cells with abundant cytoplasm that were positive for S-100 protein, melanoma antigen, and HMB-45, resulting in a diagnosis of malignant melanoma. A gastrointestinal barium study for further exploration demonstrated a filling defect 6 cm in size at the ligament of Treitz. Follow-up EGD of this finding revealed an ulcerated, half-circumferential lesion with a distinct ulcer mound extending from the ascending part of the duodenum to the jejunum, and additional biopsy also indicated malignant melanoma. Computed tomography scans showed wall thickening from the ascending part of duodenum to the proximal jejunum, whereas positron emission tomography revealed accumulation at the upper gastric body, the duodenum to the jejunum, and the left adrenal gland. Systemic exploration of the patient, including the skin, anus, and eyeballs, revealed no other lesions, and primary small intestinal malignant melanoma with metastasis to the stomach and adrenal gland was diagnosed. Partial duodenojejunectomy, partial gastrectomy, and left adrenalectomy were performed, and adjuvant chemotherapy with dacarbazine, nimustine hydrochloride, and vincristine sulfate was administered. No postoperative recurrence has been observed in the past 3 years.

In Japan, endoscopic resection (ER), including endoscopic mucosal resection and endoscopic submucosal dissection, is widely performed for superficial esophageal neoplasms and accepted as a minimally invasive treatment. Perforation is a major complication of ER, with an incidence rate of 1–5%. While conservative treatment has become a more common choice, surgical treatment of perforations is sometimes required, especially for large perforations. Of 1408 cases of esophageal ER that have been performed, 17 cases of perforation occurred at the Cancer Institute Hospital between 2005 and 2016. Most cases were treated with endoscopic clipping and managed conservatively; however, 2 cases were not eligible for endoscopic closure. We report two cases of large perforations of 15 and 20 mm, respectively. Both cases were treated conservatively with endoscopic tissue shielding, in which the perforations were covered with a large polyglycolic acid (PGA) sheet that was affixed with fibrin glue. Neither of the cases required open surgery. In both cases, feeding started three weeks after the procedure (19 and 21 days), and both were discharged within a month (29 and 30 days). In conclusion, tissue shielding with PGA sheets in large perforations after esophageal ER is a good choice to safely proceed with conservative treatment. On the other hand, endoscopic clipping is effective and reasonable for small perforations.

It is unknown whether Helicobacter pylori (H. pylori) eradication is beneficial when demarcating undifferentiated-type early gastric cancers (UD-type EGCs). This study aimed to determine whether H. pylori eradication is beneficial, and also when benefits become detectable.Sixty lesions that were detected as a ≤20-mm lesion without metastasis or ulceration on routine examination, diagnosed as UD-type EGC on biopsy, and treated with endoscopic submucosal dissection between January 2010 and January 2015 were studied. Magnifying endoscopy with narrow-band imaging (ME-NBI) was performed to demarcate the lesions. The most oral and most anal sites were marked. After endoscopic therapy, the markings were compared with the pathological examination results to calculate accurate diagnosis rates, which were compared between 27 patients with H. pylori eradication and 33 patients without. Mean intercrypt distance ratio and inflammatory cell infiltration were also compared, as were seven patients who underwent the procedure 1 month after H. pylori eradication and 20 patients who underwent the procedure more than 1 month after H. pylori eradication.Accurate diagnosis rates were 92.2% with eradication and 60.6% without. Mean intercrypt distance ratios were 1.95 and 1.59, respectively. Neutrophil infiltration was mild in the eradication group. Significant differences were observed in each parameter (p 0.05). No significant difference was observed between the 1-month eradication and1-month eradication subgroups in terms of accurate diagnosis rate, mean intercrypt distance ratio, or histological grade of any item.This study suggests that H. pylori eradication therapy aids the accurate delineation of UD-type EGC in ME-NBI.

Siewert type II esophagogastric junction adenocarcinoma encompasses both gastric cardia adenocarcinoma (GCA) and Barrett’s esophageal adenocarcinoma (BEA) due to short-segment Barrett’s esophagus. We compared these two types of Siewert type II esophagogastric junction adenocarcinoma in terms of background factors and clinical outcomes of endoscopic submucosal dissection (ESD). We enrolled 139 patients (142 lesions) who underwent ESD from 2006 to 2014 at our institution. Background factors evaluated were age, sex, body mass index, hypertension, hyperlipidemia, hyperuricemia, diabetes mellitus, smoking, drinking, double cancer, and endoscopic findings. Clinical outcomes evaluated were procedure time, en bloc resection rate, curative resection rate, and adverse events. There were 87 GCA lesions (61.2%) and 55 BEA lesions. Features of BEA [55 lesions (38.8%)] included a younger age, small diameter, and a protruding type, along with a high frequency of esophageal hiatal hernia and less mucosal atrophy. There were no significant differences in lifestyle-related background factors between the GCA and BEA groups. Curative resection rate was greater for GCA (81%) than for BEA (66%) (P = 0.01). There were no serious adverse events in either group. Among the factors for noncurative resection, lymphovascular invasion and depth of invasion were greater for BEA (33.3 vs. 7 and 20.7 vs. 8.2%, respectively (P

The incidence of esophageal adenocarcinoma (EAC) in cases with long-segment Barrett's esophagus (BE) has not been investigated in Japan. The aim of this study is to investigate the incidence of EAC in Japanese cases with long-segment BE prospectively.This is a multicenter prospective cohort study investigating the incidence rate of EAC in patients with BE with a length of at least 3 cm. Study subjects received index esophagogastroduodenoscopy at the time of enrollment, and they were instructed to undergo yearly follow-up esophagogastroduodenoscopy. Patients in whom EAC was diagnosed in the endoscopic examinations underwent subsequent treatment, and their prognosis was observed.Of 215 enrolled patients, six (2.8%) were initially diagnosed with EAC at the enrollment. Among the remaining 209 patients, 132 received at least one follow-up esophagogastroduodenoscopy. In this follow-up, three EACs developed in 251 observed patient-years (incidence rate: 1.2% per year). Most of the EACs detected at the initial endoscopic examination (5/6, 83%) were already at advanced stages. Meanwhile, all the three lesions detected in the follow-up esophagogastroduodenoscopies were identified as early cancers and subjected to curative resection.The incidence rate of EAC in Japanese cases with long-segment BE was calculated to be 1.2% in a year.

Endoscopic submucosal dissection (ESD) is minimally invasive and thus has become a widely accepted treatment for gastric neoplasms, particularly for patients with comorbidities. Antithrombotic agents are used to prevent thrombotic events in patients with comorbidities such as cardio-cerebrovascular diseases and atrial fibrillation. With appropriate cessation, antithrombotic therapy does not increase delayed bleeding in low thrombosis-risk patients. However, high thrombosis-risk patients are often treated with combination therapy with antithrombotic agents and occasionally require the continuation of antithrombotic agents or heparin bridge therapy (HBT) in the perioperative period. Dual antiplatelet therapy (DAPT), a representative combination therapy, is frequently used after placement of drug-eluting stents and has a high risk of delayed bleeding. In patients receiving DAPT, gastric ESD may be postponed until DAPT is no longer required. HBT is often required for patients treated with anticoagulants and has an extremely high bleeding risk. The continuous use of warfarin or direct oral anticoagulants may be possible alternatives. Here, we show that some antithrombotic therapies in high thrombosis-risk patients increase delayed bleeding after gastric ESD, whereas most antithrombotic therapies do not. The management of high thrombosis-risk patients is crucial for improved outcomes.

We experienced a case of gastric cancer that was prospectively followed up for 8 years. With severe heart disease, the patient did not wish surgery or anticancer drug treatment. After informed consent was obtained, he was followed up for 8 years. He received upper gastrointestinal endoscopy every year, which revealed IIc early gastric cancer, and biopsy showed well differentiated adenocarcinoma. A flat and mildly depressed lesion with redness was observed on endoscopy, exhibiting typical morphology of IIc-type early gastric cancer. The appearance of IIc M cancer was observed macroscopically from 2000 to 2003. Four years later, surface irregularity with ulceration appeared. Then, the whole lesion was elevated, which suggested submucosal invasion, and the tumor exhibited the morphology of IIa + IIc or type 3. The ulcer became deeper and elevated boundaries were formed. Horizontal expansion of the flat lesion was mild, while invasion to deeper layers was predominant. Eventually, he died of heart failure. Estimated M cancer was observed for about 3 years, followed by invasion to deeper layers. Taken together, this is a valuable case that followed up the manner of invasion to deeper layers over time from early to advanced gastric cancer.

Aim: Endoscopic submucosal dissection (ESD) is relatively difficult compared with endoscopic mucosal resection (EMR), thus, proper training is essential for the safe performance of the procedure. The aim of this study is to clarify the current status of training for ESD for gastric epithelial neoplasm by following the performance of 13 preceptees. Methods: We performed ESD for 1520 lesions between March 2005 and April 2011 and conducted ESD training of 13 preceptees who were supervised by experts. We classified the samples into four groups according to the number of ESD performed by the preceptees to chart their progress by comparing the procedural outcomes. Group A included cases 1–40 performed by all 13 preceptees, group B consisted of cases 41–80 performed by 10 of the preceptees and group C included cases 81 onwards executed by five of the preceptees. Group D comprised the cases that were performed by experts during the same period as group C. Results: The procedural outcomes of group A were similar to those of group B with regard to operation time, complete en bloc resection and complications. However, the results of group B included significantly more lesions of the middle or upper third of the stomach, resected specimen and lesions were larger in diameter, lesions with positive ulcer finding were more frequent and a higher frequency of lesions were of expanded, non-indication type. Group B outcomes were similar to those of group C but differed in location of lesions and specimen size. Group C outcomes were similar to group D's in all parameters. Conclusion: Preceptees were able to safely perform ESD for gastric epithelium neoplasms under appropriate supervision by expert endoscopists. The number of cases in which preceptees successfully extracted guideline-indication lesions and expanded-indication lesions by ESD were approximately 40 and 80 cases, respectively. The procedural outcomes of ESD performed by preceptees who had experience in over 80 cases were similar to those by expert endoscopists. Thus, these findings show that the minimal amount of training for achieving preceptorship of ESD is performance of at least 80 of the procedures.

Aim: The aim of this study was to elucidate characteristics of gastric lesions that are initially diagnosed as low-grade adenomas and to establish appropriate treatment. Methods: We retrospectively reviewed 231 lesions initially diagnosed as gastric adenomas. All forceps biopsy samples were histologically diagnosed as category 3 low-grade adenomas according to the revised Vienna Classification. All patients underwent endoscopic resection with endoscopic findings and post-resection diagnoses evaluated subsequently. Results: Sixty-three lesions were initially diagnosed as depressed adenomas, and 168 lesions were diagnosed as protruding adenomas. The depressed lesions were significantly smaller (11.6 ± 5.0 mm) than the protruding lesions (17.0 ± 10.8 mm) (P

Background and study aim: Endoscopic submucosal dissection (ESD) of undifferentiated-type early gastric cancer (UD-EGC) is technically feasible; however, the long-term clinical outcomes of the procedure have not yet been fully investigated. The aim of our study was to elucidate long-term outcomes of ESD for UD-EGC. Patients and methods: Between September 2003 and October 2009, a total of 153 patients were diagnosed endoscopically as having UD-EGC fulfilling the expanded criteria for ESD. After informed consent was obtained, 101 patients were selected to undergo ESD and 52 to undergo surgical operation. We assessed the clinical outcomes of ESD in 101 consecutive patients with 103 UD-EGC lesions who were undergoing ESD for the first time. The overall mortality and disease-free survival rates after ESD were evaluated as the long-term outcomes. Results: The rates of en bloc and curative resection were 99.0 % (102 /103) and 82.5 % (85 /103), respectively. We encountered one patient with nodal metastasis detected by computed tomography before diagnostic ESD, although curative resection of the primary lesion was achieved based on routine histological examination. Among the 78 patients without a past history of malignancy within the previous 5 years in whom curative resection of the primary lesion was achieved, no cases of local recurrence or distant metastasis were observed during follow-up; however, 1 synchronous and 2 metachronous lesions were detected in 2 patients (2.6 %) after primary ESD. Thus, estimated over a median follow-up period of 40.0 months (range 19 – 92 months) and 36.0 months (range 9 – 92 months), the 3 – and 5-year overall mortality rates were 1.9 % and 3.9 %, respectively, and the 3 – and 5-year overall disease-free survival rates were both 96.7 %. Conclusions: Although our single-center retrospective study may be considered to be only preliminary, our data indicate that ESD for UD-EGC may yield good long-term outcomes.

Background and Aims: The diagnostic use of magnification endoscopy with narrow-band imaging (ME-NBI) to assess histopathologically undifferentiated-type early gastric cancers (UD-type EGCs) is not well elucidated. The purpose of this study was to examine the comparative relationship between ME-NBI images and histopathological findings in UD-type EGCs. Methods: We analyzed 78 consecutive cases of UD-type EGCs ≤ 20 mm in diameter that underwent ME-NBI ≤ 2 weeks prior to resection. The ME-NBI images were compared with histopathological findings following either endoscopic submucosal dissection (ESD) or surgery. Applying the comparative results, we prospectively evaluated the success of identifying the lateral extent of UD-type EGCs resected by ESD in additional consecutive cases. Results: Lesions with preserved but irregular surface microstructures (S-type based on ME-NBI) showed mucosal atrophy and corresponded histologically to the non-whole-layer type of intramucosal cancer (24/24, 100%). Lesions with an irregular microvasculature type (V-type, for example, corkscrew pattern) or mixed type upon ME-NBI corresponded histopathologically to the non-whole-layer type of intramucosal cancer (15/54, 27.8%), the whole-layer type of intramucosal cancer (27/54, 50.0%) or submucosal (sm) invasion cancer (12/54, 22.2%). Applying these comparative results, we used ME-NBI to successfully predict the lateral extent of cancer, which corresponded to the histopathological lateral extent in all 18 additional consecutive UD-type EGCs resected by ESD. Conclusions: ME-NBI images of UD-type EGCs were very closely related to the histopathological findings. Thus, ME-NBI can be useful in the pretreatment assessment of the histopathological patterns of cancer development and the lateral extent of such lesions.

The results of a phase III, placebo-controlled study demonstrated that endoscopic direct spraying of L: -menthol onto the gastric mucosa effectively suppressed gastric peristalsis in the study patients. The aim of the study reported here was to determine whether the anti-peristaltic effect of an L: -menthol preparation facilitates endoscopic examinations in a clinical setting.This was a multicenter, open-label, single-arm trial in which the study cohort comprised patients in whom L: -menthol was likely to be used to facilitate endoscopic examination in clinical settings. The primary outcome was the proportion of subjects with no peristalsis (Grade 1) after treatment and at the end of endoscopy (defined as the complete suppression of gastric peristalsis). This variable was assessed according to the level of anti-Helicobacter pylori immunoglobulin G (IgG) antibody, pepsinogen test results, whether sedation was performed, and whether subjects were considered unsuitable for the use of conventional antispasmodics.Of the 119 enrolled subjects, data from 112 were included in the primary efficacy analysis. Gastric peristalsis was completely suppressed in 37.5% of the patients [42/112 patients; 95% confidence interval (CI) 28.5-47.1]. Subgroup analyses revealed that the rate of peristalsis suppression was significantly higher in patients with elevated levels of anti-H. pylori IgG antibody (26/44, 59.1%; 95% CI 43.2-73.7); P 0.001] and positive pepsinogen test results (21/35, 65.6%; 95% CI 46.8-81.4; P 0.001]. There was no significant difference according to sedation (17/52, 32.7%; 95% CI 20.3-47.1; P = 0.434) or whether subjects were considered unsuitable for use of conventional antispasmodic agents (14/28, 50.0%; 95% CI 30.6-69.4; P = 0.12].These findings are comparable to those of the phase III placebo-controlled study and provide further evidence that endoscopic direct spraying of L: -menthol effectively suppresses gastric peristalsis during upper gastrointestinal endoscopy.

Although sporadic nonampullary duodenal adenoma (SNDA) is regarded as a precancerous lesion, its natural course is uncertain. The aim of this study was to evaluate the risk of development of adenocarcinoma in SNDA lesions initially diagnosed as showing low-grade dysplasia (LGD; category 3) or high-grade dysplasia (HGD; category 4.1).We analyzed 68 SNDAs, diagnosed based on initial and subsequent biopsies, in 66 consecutive patients. Of these, 46 (43 LGD lesions, 3 HGD lesions) were followed up for ≥6 months without treatment (mean 27.7±16.9 months; range 6-72 months), including 8 lesions that were eventually resected during follow-up. Sixteen lesions (eight LGD lesions, eight HGD lesions) were resected immediately, either endoscopically or surgically, and six lesions were excluded because of a short follow-up (6 months). The histopathological diagnoses and macroscopic changes were evaluated.Among the 43 LGD lesions followed up for ≥6 months, 34 (79.1%) showed no histopathological changes during follow-up, whereas the remaining 9 (20.9%) showed progression to HGD, including 2 (4.7%) that progressed eventually to noninvasive carcinoma (category 4.2). Macroscopically, 76.7% (33 of 43) of the LGD lesions showed no notable changes in size, 16.3% (7 of 43) became undetectable, 4.7% (2 of 43) reduced in size, and 2.3% (1 of 43) became larger in size. In contrast, all the three HGD lesions that were followed up for ≥6 months remained unchanged histologically, based on biopsy, and showed no notable macroscopic changes, although one of these HGD lesions resected endoscopically revealed evidence of noninvasive carcinoma. Although we diagnosed all lesions as HGD from biopsy samples, a high percentage of cancers (54.5%, 6 of 11) were diagnosed from resected specimens. A multivariate analysis identified HGD diagnosed at first biopsy and a lesion diameter of ≥20 mm as being significantly predictive of progression to adenocarcinoma.LGD lesions show a low risk of progression to adenocarcinoma, but some risk of progression to HGD, which warrants careful follow-up biopsy. However, HGD lesions and large SNDAs≥20 mm in diameter show a high risk of progression to adenocarcinoma. Therefore, they should be treated immediately.

A new rendezvous-style surgical technique has been developed to ensure the safety of endoscopic submucosal dissection (ESD) for duodenal tumors. The new technique, called "laparoscopic-endoscopic cooperative surgery (LECS)," combines ESD with laparoscopic, reinforcing, seromuscular suturing. This case series report describes how three patients with a duodenal tumor were safely treated by LECS. ESD was performed by endoscopy, followed by closure of the mucosal defect using seromuscular suturing by laparoscopy. ESD was successfully completed in all patients. Endoscopic findings after suturing revealed that the mucosal defect was closed appropriately and tightly. None of the three patients experienced delayed perforation or stricture after LECS. LECS for extraction of duodenal tumors seems to be feasible and helps to ensure the safety of ESD in the duodenum.

Background Excessive visceral fat might promote cancer development and progression because of metabolic disruption. A previous study has demonstrated that visceral obesity associated with lymphatic invasiveness and a poor response to preoperative treatment among patients who underwent esophagectomy for advanced esophageal squamous cell carcinoma (ESCC). This study aimed to clarify the impact of abdominal fat distribution on lymphatic and vessel invasion after endoscopic submucosal dissection (ESD) or esophagectomy for early ESCC (eESCC). Methods We enrolled the 106 patients who had undergone ESD or curative esophagectomy for pathological T1-muscularis mucosa (MM) and T1-submucosal layer (SM) lesions between January 2015 and December 2016. Using computed tomography volumetry, we measured areas of visceral (VFA) and subcutaneous (SFA) fat at the level of the umbilicus, and calculated the VFA/SFA ratio in each patient. We also measured body mass index (BMI). Lymphatic and vessel invasion by eESCC were compared with these parameters and between groups classified according to VFA/SFA ratios. Results Significantly more patients in the T1-MM group with high VFA/SFA had lymphatic invasion of eESCC compared with those who had low VFA/SFA (35.7% vs. 7.1%, P = 0.010). Metastatic lymph nodes were detected only in patients with high VFA/SFA who underwent esophagectomy. Values for BMI, VFA, and SFA were lower in patients with venous invasion than those without (BMI, 20 vs. 22.8, P = 0.076; VFA, 60.2 vs. 98.9 cm2, P = 0.042; SFA, 56.3 vs. 103.2 m2, P Conclusion High VFA/SFA ratio was significantly associated with lymphatic invasion in patients with eESCC. Low values of BMI, VFA, and SFA was significantly associated with venous invasion in patients with eESCC. Abdominal fat distribution might influence lymphatic and vessel invasion by eESCC. Disclosure All authors have declared no conflicts of interest.

Background We have reported that lymph node metastasis risk in cases of superficial Barrett's esophageal cancer (BC) was of submucosal invasion within 500μm without other risk factors (lymphovascular involvement, a poorly differentiated component, and lesion size) through a multicenter retrospective study in 13 facilities. Cardiac cancer (CC) was included in the gastric cancer criteria of the Japanese Gastric Cancer Association. Since BC and CC near the esophagogastric junction (EGJ) show almost the same biological behavior, we elucidated the metastasis risk factors in patients with EGJ adenocarcinoma. Methods Patients who underwent ESD for superficial EGJ adenocarcinoma as Siewert typeII between January 2011 and April 2017 were included. Results A total of 120 patients were analyzed. Fifty-three patients (44.1%) had BC and 67 patients (55.8%) had CC. Of the 120 lesions, the median size was 16.7 ± 8.5 mm; 10 (8.3%; 4 BC, 6 CC) were greater than 30 mm in size. Thirty-five (29.1%; 17 BC, 18 CC) were submucosal (SM) cancers. Twenty-one (17.5%; 13 BC, 8 CC) had poorly differentiated components and 19 (15.8%; 14 BC, 5 CC) had lymphovascular involvement. Of the 19 cases with lymphovascular involvement, 11/22 (50%) were SM cancers with > 200μm of invasion, and 8/98 (8.1%) were mucosal (M)/SM cancers within SM200μm of invasion. Of the BCs with DMM invasion, 7/17 (41.1%) had lymphovascular involvement. Of the patients initially treated through ESD, 33 (27.5%) had lymphovascular involvement, positive horizontal/vertical margins, or SM > 200μm of invasion. Of these, 26 were treated with additional surgery. Metastasis was confirmed from 2 patients. Both were BCs, with SM > 501μm of invasion, positive lymphovascular involvement, and with poorly differentiated components. One was > 30 mm in size. Metastasis was not identified in CC and in cases with SM Conclusion For superficial esophagogastric cancer, we did not identify metastasis in patients with SM > 501 μm of invasion. There were no cases of metastasis in patients without risk factors. ESD might be indicated for lesions within SM 500μm of invasion without risk factors. Among DMM cases of BC, lymphovascular involvement was highly frequent. Therefore, histopathological surveillance for lymphovascular involvement is important. Disclosure All authors have declared no conflicts of interest.

Background Barrett's esohageal adenocarcinoma(BEA) originated from Long-segment Barrett's esophagus(LSBE) were found to be larger lesions than BEA from Short-segment Barrett's esophagus(SSBE). In Japan, superficial BEA were found and treated by ESD. However, most of superficial BEA in Japan are originated from SSBE. We investigated about the differences between BEA from SSBE and LSBE. Methods We examined macroscopic appearance and histology for superficial BEA. And we compared with BEA between SSBE and LSBE.And then we examined imminohistochemical study using p53 for operated specimens of superficial BEA. Results The multiple lesions were presented only LSBE cases. Operations were the far more common treatment for LSBE. The ratio of lesions involving more than one-half of the lumen was significantly larger in LSBE cases. The percentage of type 0-IIb was only 3.2%(3/95) for SSBE, whereas 32.6%(15/46) for LSBE (P Conclusion Most superficial BEA originated from SSBE could be distinguished by the elevated lesions. Whereas, in cases of LSBE, flat type lesions including the accompanied type 0- IIb and multiple lesions, operation cases, the ratios of lesions involving a large range and the complex macroscopic types were significantly higher. When we diagnose and treat superficial BEA, it is necessary to consider the differences between SSBE and LSBE, such as macroscopic types. Disclosure All authors have declared no conflicts of interest.

Delayed bleeding is one of the major complications of endoscopic submucosal dissection (ESD). The aim of this study is to determine the incidence rate and clinical factors associated with delayed bleeding¸ as well as the time interval between bleeding and ESD for gastric neoplasm. We investigated 647 lesions in 582 consecutive patients undergoing ESD for gastric neoplasm. Delayed bleeding after ESD was evident in all 28 lesions from 28 patients (4.33% of all specimens, 4.81% of patients), and all achieved endoscopic hemostasis. Resected specimen width (≥40 mm) was the only significant factor associated with delayed bleeding on univariate and multivariate analysis. In early delayed bleeding (bleeding occurring on or before the fourth postoperative day), wide resected specimen and tumor location in the lower third of the stomach were significant risk factors. In late delayed bleeding (bleeding occurring after the fifth operative day), wide resected specimen, tumor location in the middle third of the stomach, hypertension, and high body mass index (≥25 kg/m2) were significant factors. Delayed bleeding in patients with tumors in the upper and middle third of the stomach (median 8.0 days; range 1–20 days) occurred significantly later as compared with patients who had tumors in the lower third (median 2.0 days; range 1–34 days). Risk factors for delayed bleeding, and the probable underlying mechanism involved, differed depending on the time elapsed between surgery and the bleeding episode.

Aim: The aim of the present study was to examine therapeutic outcomes of endoscopic submucosal dissection (ESD) of undifferentiated-type intramucosal gastric cancer and the problems of diagnosis. Methods: We reviewed 58 patients with preoperatively diagnosed undifferentiated-type intramucosal early gastric cancer (EGC) without ulceration with a diameter of 20 mm or smaller (expanded-indication lesion) who underwent ESD at the Cancer Institute Hospital between September 2003 and August 2008. Results: The overall rates of one-piece resection and complete resection were 98% and 90% respectively, and the median operation time was 70 min. Bleeding was seen in 8.6% and perforation in 3.4%. The curative resection rate was low at 79%. Factors responsible for non-curative resection were most commonly submucosal invasions. If limited to pathologically diagnosed expanded-indication lesions, the curative resection rate was 98%. The difference in tumor size between a macroscopic diameter and a histological diameter was within ±5 mm in 96% of expanded-indication lesions, with none of these cases having a histological diameter that exceeded the macroscopic diameter by more than 5 mm. Conclusion: ESD was technically feasible for expanded-indication lesions of undifferentiated-type EGC. We achieved a high rate of curative resection by the markings at sites 5 mm beyond the preoperatively determined lesion area. Factors responsible for non-curative resection were most commonly submucosal invasions. We should diagnose the depth of such lesions more carefully.

Endoscopic resection (ER) has been accepted as minimally invasive treatment in patients with early gastric cancer (EGC) who have a negligible risk of lymph node metastasis. It has already been determined which lesions in differentiated-type EGC present a negligible risk of lymph node metastasis, and ER is being performed for these lesions. In contrast, no consensus has been reached on which lesions in undifferentiated-type (UD-type) EGC present a negligible risk for lymph node metastasis, nor have indications for ER for UD-type EGC been established.We investigated 3843 patients who had undergone gastrectomy with lymph node dissection for solitary UD-type EGC at the Cancer Institute Hospital, Tokyo, and the National Cancer Center Hospital, Tokyo. Seven clinicopathological factors were assessed for their possible association with lymph node metastasis.Of the 3843 patients, 2163 (56.3%) had intramucosal cancers and 1680 (43.7%) had submucosal invasive cancers. Only 105 (4.9%) intramucosal cancers compared with 399 (23.8%) submucosal invasive cancers were associated with lymph node metastases. By multivariate analysis, tumor size 21 mm or more, lymphatic-vascular capillary involvement, and submucosal penetration were independent risk factors for lymph node metastasis (P0.001, respectively). None of the 310 intramucosal cancers 20 mm or less in size without lymphatic- vascular capillary involvement and ulcerative findings was associated with lymph node metastases (95% confidence interval, 0-0.96%).UD-type intramucosal EGC 20 mm or less in size without lymphatic-vascular capillary involvement and ulcerative findings presents a negligible risk of lymph node metastasis. We propose that in this circumstance ER could be considered.

We aimed to clarify the frequency and clinicopathological characteristics of gastric stump carcinoma following proximal gastrectomy.Three-hundred and sixteen patients who had undergone curative proximal gastrectomy over a 21-year period from January 1984 through December 2004 were reviewed.Gastric stump carcinoma was observed in 17 patients (5.4%). The time interval between the initial gastrectomy and the treatment of gastric stump cancer was within 5 years in 3 patients, within 5-10 years in 8, and after 10 years in 6. Treatment included endoscopic resection (n = 4), completion total gastrectomy of the remnant stomach (n = 11), pancreatoduodenectomy (n = 1), and nonsurgical resection (n = 1). Pathologically, 9 carcinomas were differentiated and 8 were undifferentiated. In a review of reconstruction methods associated with disease stage, stage I was found in 6 of the 7 patients with esophagogastrostomy or short-segment jejunal interposition. On the other hand, stage I was found in only 3, but stage II-IV was found in 7 of the 10 patients with reconstruction by double-tract or long-segment jejunal interposition; thus, the tumor was more likely to be detected at an advanced stage after long-segment interposition (P = 0.049).Gastric stump carcinoma following proximal gastrectomy occurred at a high frequency of 5.4% of initial resections. It is necessary to select a reconstruction method that facilitates postoperative endoscopic examination, as well as to follow up the patients after proximal gastrectomy in the long term for the early detection and early treatment of gastric stump carcinoma.

Currently, transnasal esophagogastroduodenoscopy using an ultrathin endoscope is being widely carried out as a screening test for early gastric cancer. We compared the diagnostic utility of ultrathin esophagogastroduodenoscopy with that of conventional esophagogastroduodenoscopy in detecting 42 lesions of early gastric cancer that had a diameter of

Background: Superficial Barrett’s esophageal adenocarcinoma (s-BEA) in Barrett’s esophagus frequently occurs in the right wall of the esophagus. Our aim was to examine the correlation between the location of s-BEA and the direction of acid and non-acid reflux in patients with Barrett’s esophagus. Patients and methods: We performed 24-h pH monitoring in 33 s-BEA patients using a pH catheter with eight sensors. One sensor was located at the 6 o’clock position in the lower esophagus and sensors 1 – 8 were arranged counterclockwise at the same level. The catheter was positioned at the same level as the s-BEA. We measured the maximal total duration of acid (MTD-A) and non-acid (MTD-NA) reflux. When the direction of MTD-A and MTD-NA coincided with the location of the s-BEA, the case was defined as coincidental and we calculated the rate of coincidence, and the probability of the rate of coincidence was estimated with 95 % confidence intervals (95 %CI). Results: Among the 33 cases of s-BEA examined, the rate of coincidence of both MTD-A and MTD-NA was 24/33 (72.7 %) (95 %CI 0.54 – 0.87). The rate of coincidence of either MTD-A or MTD-NA was 30/33 (90.9 %) (95 %CI 0.76 – 0.98). Conclusions: Our study revealed that the location of s-BEA mostly corresponds to the direction of MTD-A or MTD-NA. Accurate observation of the distribution of acid or non-acid reflux by pH monitoring would aid early detection of s-BEA by endoscopy.

Sessile serrated adenoma/polyps (SSAPs) are suspected to have a high malignant potential, although few reports have evaluated the incidence of carcinomas derived from SSAPs using the new classification for serrated polyps (SPs). The aim of study was to compare the frequency of cancer coexisting with the various SP subtypes including mixed polyps (MIXs) and conventional adenomas (CADs). A total of 18,667 CADs were identified between April 2005 and December 2011, and 1858 SPs (re-classified as SSAP, hyperplastic polyp (HP), traditional serrated adenoma (TSA), or MIX) were removed via snare polypectomy, endoscopic mucosal resection, or endoscopic sub-mucosal dissection. Among 1160 HP lesions, 1 (0.1 %) coexisting sub-mucosal invasive carcinoma (T1) was detected. Among 430 SSAP lesions, 3 (0.7 %) high-grade dysplasia (HGD/Tis) and 1 (0.2 %) T1 were detected. All of the lesions were detected in the proximal colon, with a mean tumor diameter of 18 mm (SD 9 mm). Among 212 TSA lesions, 3 (1 %) HGD/Tis were detected but no T1 cancer. Among 56 MIX lesions, 9 (16 %) HGD/Tis and 1 (2 %) T1 cancers were detected, and among 18,677 CAD lesions, 964 (5 %) HGD/Tis and 166 (1 %) T1 cancers were identified. Among the resected lesions that were detected during endoscopic examination, a smaller proportion (1 %) of SSAPs harbored HGD or coexisting cancer, compared to CAD or MIX lesions. Therefore, more attention should be paid to accurately identifying lesions endoscopically for intentional resection and the surveillance of each SP subtype.

In Japan, the criteria for cancer of the esophagogastric junction (EGJ) are that the center of the lesions are located within 2cm from the EGJ orally and anally. The main histology of these lesions are squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma of the esophagus is treated following the guidelines published by the Japan Esophageal Society. This paper focuses on EGJ adenocarcinomas, which include cardiac gastric cancer and Barrett's cancer originating from the short-segment Barrett's esophagus. EGJ cancer is resected endoscopically at the termination of the palisade vessels or upper end of the gastric fold. The various types of cancer involving the EGJ are treated following the guidelines published by each medical specialist society in Japan. The main endoscopic treatment is endoscopic submucosal dissection. The EGJ is a narrow space, and therefore lesions are approached from the oral approach or anal approach using a reverse endoscope. Bleeding, perforation, and stenosis are major complications. When two-thirds or more of the wall is resected, stenosis occurs. Endoscopic therapy for cancer originating in the EGJ has not yet been fully established.

Endoscopic submucosal dissection (ESD) is useful as a minimally invasive treatment option for early gastric cancer. ESD is also used in the management of postoperative remnant gastric cancers in the stomach and gastric tube cancers. Perforation and delayed bleeding have been the main complications of ESD reported in the management of gastric tube cancer. However, in the current literature, there is no description of precordial skin burns caused by electrical coagulation.While we treated 22 patients with gastric tube cancers by ESD from 2005 to 2014, we experienced five skin burns in four patients after ESD. We retrospectively analyzed clinical characteristics of precordial skin burn as a complication of ESD.All skin burns occurred in patients reconstructed using a presternal route, whose incidence of precordial skin burn was 55.6%. In all cases, lesions were located in the upper or middle third of gastric tubes irrespective of their direction. Skin burn developed on postoperative day (POD) 1 or POD 2, taking 4-7 days to heal and was accompanied by high fever in 60% of cases.The present study suggests that when carrying out ESD for gastric tube cancer using the presternal route, it is necessary to consider the occurrence of a precordial skin burn as a possible complication.

Diagnostic endoscopy occasionally shows synchronous early gastric cancer (EGC) and esophageal cancer (EC) in the same patient. The treatment plan for these comorbid cancers is unclear because, as EGC is commonly treated surgically, information on post-chemotherapy outcomes for EGC are lacking, although chemotherapy and chemoradiotherapy are important in treating EC. Here, we evaluated whether unresected EGC could be safely observed while synchronous EC is treated with chemotherapy in patients with both cancers. We enrolled 30 patients with both EGC and EC who were treated with 5-FU plus cisplatin (FP) from January 2006 to September 2013, and who were evaluated with endoscopy before chemotherapy, and approximately every 3 months afterwards. The response rate to FP for EGC was 46.8 %. Notably, five cases (16.7 %) had clinically complete responses with no progressive disease. Progression-free survival was 100 % at 6 months and 96.2 % at 1 year. In univariate analysis, FP was significantly more effective for mixed-type and undifferentiated adenocarcinoma than for differentiated adenocarcinoma. FP was effective for EGC. EGC was stable without progression for more than 6 months while patients underwent FP treatment for EC. We consider observing EGC with no treatment during chemotherapy for EC to be appropriate disease management.

The reported outcomes of endoscopic resection (ER) for early gastric cancer (EGC) remain limited to several single-institution studies.A multicenter retrospective study was conducted at 11 Japanese institutions concerning their results for ER, including conventional endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).A total of 714 EGCs (EMR, 411; ESD, 303) in 655 consecutive patients were treated from January to December 2001. Technically, 511 of the 714 (71.6%) lesions were resected in one piece. The rate of one-piece resection with ESD (92.7%; 281/303) was significantly higher compared with that for EMR (56.0%; 230/411). Histologically, curative resection was found in 474 (66.3%) lesions. The rate of curative resection with ESD (73.6%; 223/303) was significantly higher compared with that for EMR (61.1%; 251/411). Blood transfusion because of bleeding was required in only 1 patient (0.1%) with EMR of 714 lesions. Perforation was found in 16 (2.2%). The incidence of perforation with ESD (3.6%; 11/303) was significantly higher than that with EMR (1.2%; 5/411). All complications were managed endoscopically, and there was no procedure-related mortality. The median follow-up period was 3.2 years (range, 0.5-5.0 years). In total, the 3-year cumulative residual-free/recurrence-free rate and the 3-year overall survival rate were 94.4% and 99.2%, respectively. The 3-year cumulative residual-free/recurrence-free rate in the ESD group (97.6%) was significantly higher than that in the EMR group (92.5%).ER leads to an excellent 3-year survival in clinical practice and could be a possible standard treatment for EGC. ESD has the advantage of achieving one-piece resection and reducing local residual or recurrent tumor.

Background. Although the number of patients with early gastric cancer (EGC) treated by endoscopic mucosal resection (EMR) has increased, the appropriate strategy for treating those with incomplete resection has not been established. Methods. This study analyzed 726 cases of EGC in patients treated by EMR between 1991 and 2000, in order to clarify the en-bloc and complete resection rates. We classified patients with incomplete resection into four groups according to the estimated risk of residual cancer or lymph node (LN) metastasis, determined from pathological findings of EMR specimens. We then analyzed 45 patients with EGC treated surgically after incomplete EMR, with the aim of eliciting the risk of residual cancer and LN metastasis. Results. Of the 726 patients, 529 (72.9%) had an en-bloc resection, while 378 (52.1%) had a complete resection. Three hundred and nine patients were found to have mucosal cancer and lateral cut-end-positive status with no LN metastasis (group A). In this group, 18 patients (5.8%) had residual cancer, with the lesions in the majority of patients being limited to the mucosal layer. Group B consisted of 14 patients with differentiated and submucosal (sm1) depth cancers, with 1 patient having residual cancer and 2 patients having LN metastasis. Fifteen patients were classified as group C, with sm2 or greater and vertical cut end-negative status, with 2 showing residual cancer and 1 showing LN metastasis. Group D included 10 patients with vertical cut end-positive status. Four of these patients had residual cancer while 1 had LN metastasis. Conclusion. We recommend that patients in group A should have close follow-up or endoscopic treatment, while those in groups B, C, or D should be treated by gastrectomy associated with LN dissection.