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Narrow‐band imaging combined with magnified endoscopy has enabled the detection of superficial squamous cell carcinoma of the head and neck (SSCCHN) that has been resected with minimally invasive treatment, preserving vocalization and swallowing functions. However, risk factors of lymph node metastasis (LNM) must be identified, as some patients with LNM have a poor prognosis. From an initial 599 patients with 700 lesions who underwent trans‐oral surgery in 27 Japanese hospitals (a nationwide registration survey), we enrolled 541 patients with 633 SSCCHNs, as indicated by central pathological diagnoses. All pathological specimens for each patient were examined using 20 pathological factors that are thought to affect the LNM of SSCCHN. In all, 24 (4.4%) of the 568 SSCCHNs exhibited LNM, and all 24 had at least one solitary nest of epithelial neoplastic cells present in the stroma, clearly separated from the intraepithelial carcinoma. Multivariate analysis also showed that tumor thickness (p = 0.0132, RR: 7.85, 95% confidence interval [CI]: 1.54–40.02), and an INFc pattern classified as infiltrating growth (INF) with unclear boundaries between tumor and non‐tumor tissues (p = 0.0003, RR: 14.47, 3.46–60.46), and tumor budding (p = 0.0019, RR: 4.35, CI: 1.72–11.01) were significantly associated with LNM. Solitary nests may be indicative of LNM. In addition, tumor thickness was revealed to be a risk factor for LNM in SSCCHNs using pT factors that do not include an invasion depth element because of the anatomical absence of the muscularis mucosae. [ABSTRACT FROM AUTHOR]

Background: In older patients, esophageal squamous cell carcinoma (ESCC) is difficult to treat using standard therapies, including surgery and cisplatin-based chemoradiotherapy. Paclitaxel (PTX) has radiosensitizing activity. We conducted a phase I trial of PTX combined with radiotherapy to establish a standard therapy for locally advanced ESCC in older patients. Methods: Enrollment was conducted at six centers in Japan from April 2016 to September 2019. The participants were aged ≥ 70 years, had locally advanced ESCC, and were intolerant to surgery or unwilling. A fixed 60-Gy radiation dose was administered in 30 fractions. PTX dosing levels started at 30 mg/m2 weekly for 6 weeks. Depending on the number of DLTs, the dose was set to be increased by 10 mg/m2 or switched to biweekly. A geriatric assessment was performed before treatment using the Geriatric-8 screening tool. The primary endpoint was dose-limiting toxicity (DLT). Results: We enrolled 24 patients (6 per group); DLT was observed in one (grade 4 hypokalemia), one (grade 3 aspiration), two (grade 3 radiodermatitis, grade 3 esophageal hemorrhage), and two (grade 3 anorexia, grade 5 pneumonitis) patients in the weekly PTX 30, 40, 50, and 60 mg/m2 groups, respectively. All adverse events, except death in the 60 mg/m2 group, showed reversible improvement, and the safety profile was considered acceptable. The 2-year survival and complete response rates were 40.0% and 54.2%, respectively. There was a significant difference in survival between favorable and unfavorable Geriatric-8 scores. Conclusions: The recommended PTX dose with concomitant radiation was determined to be 50 mg/m2 weekly. Phase II trials at this dose are underway. [ABSTRACT FROM AUTHOR]

In Japan, standard of care of the patients with resectable esophageal cancer is neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients unfitted for surgery or with unresectable locally advanced esophageal cancer are generally indicated with definitive chemoradiotherapy (CRT). Local disease control is undoubtful important for the management of patients with esophageal cancer, therefore endoscopic evaluation of local efficacy after non-surgical treatments must be essential. The significant shrink of primary site after NAC has been reported as a good indicator of pathological good response as well as favorable survival outcome after esophagectomy. And patients who could achieve remarkable shrink to T1 level after CRT had favorable outcomes with salvage surgery and could be good candidates for salvage endoscopic treatments. Based on these data, "Japanese Classification of Esophageal Cancer, 12th edition" defined the new endoscopic criteria "remarkable response (RR)", that means significant volume reduction after treatment, with the subjective endoscopic evaluation are proposed. In addition, the finding of local recurrence (LR) at primary site after achieving a CR was also proposed in the latest edition of Japanese Classification of Esophageal Cancer. The findings of LR are also important for detecting candidates for salvage endoscopic treatments at an early timing during surveillance after CRT. The endoscopic evaluation would encourage us to make concrete decisions for further treatment indications, therefore physicians treating patients with esophageal cancer should be well-acquainted with each finding. [ABSTRACT FROM AUTHOR]

Background: Multiple development of squamous cell carcinoma (SCC) in the upper aerodigestive tract has been explained by the 'field cancerization phenomenon' associated with alcohol drinking. Squamous dysplastic lesion is clinically visualised as a Lugol-voiding lesion (LVL) by chromoendoscopy. Whether cessation or reduction of alcohol drinking improves multiple LVL and reduces the risk of field cancerization has not been elucidated. Methods: We analysed 330 patients with newly diagnosed superficial esophageal SCC (ESCC) enrolled in the cohort study. The grade of LVL was assessed in all patients every 6 months. We instructed the patients to stop smoking and drinking and recorded their drinking and smoking status every 6 months. Results: Among 330 patients, we excluded 98 with no LVL or no drinking habit. Of the remaining 232 patients, 158 continuously ceased or reduced their drinking habit. Patients who ceased or reduced their drinking habit significantly showed improvement in the grade of LVL. Multivariate analysis showed that continuous cessation or reduction of drinking habit improved the grade of LVL (hazard ratio [HR] = 8.5, 95% confidence interval [CI] 1.7–153.8, p = 0.0053). Higher grade of LVL carried a high risk of multiple ESCC and head and neck SCC (HNSCC) (HR = 3.7, 95% CI 2.2–6.4, p < 0.0001). Improvement in LVL significantly decreased the risk of multiple ESCC and HNSCC (HR = 0.2, 95% CI 0.04–0.7, p = 0.009). Conclusions: This is the first report indicating that field cancerization was reversible and cessation or reduction of drinking alcohol could prevent multiple squamous dysplastic lesion and multiple ESCC and HNSCC development. Clinical trials registry number: UMIN000001676. [ABSTRACT FROM AUTHOR]

Despite advanced therapeutics, esophageal squamous cell carcinoma (ESCC) remains one of the deadliest cancers. Here, we propose a novel therapeutic strategy based on synthetic lethality combining trifluridine/tipiracil and MK1775 (WEE1 inhibitor) as a treatment for ESCC. This study demonstrates that trifluridine induces single‐strand DNA damage in ESCC cells, as evidenced by phosphorylated replication protein 32. The DNA damage response includes cyclin‐dependent kinase 1 (CDK1) (Tyr15) phosphorylation as CDK1 inhibition and a decrease of the proportion of phospho‐histone H3 (p‐hH3)‐positive cells, indicating cell cycle arrest at the G2 phase before mitosis entry. The WEE1 inhibitor remarkedly suppressed CDK1 phosphorylation (Try15) and reactivated CDK1, and also increased the proportion of p‐hH3‐positive cells, which indicates an increase of the number of cells into mitosis. Trifluridine combined with a WEE1 inhibitor increased trifluridine‐mediated DNA damage, namely DNA double‐strand breaks, as shown by increased γ‐H2AX expression. Moreover, the combination treatment with trifluridine/tipiracil and a WEE1 inhibitor significantly suppressed tumor growth of ESCC‐derived xenograft models. Hence, our novel combination treatment with trifluridine/tipiracil and a WEE1 inhibitor is considered a candidate treatment strategy for ESCC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the risk factors for developing metachronous primary Gastric Cancer (GC) after Endoscopic Resection (ER) for esophageal Squamous Cell Carcinoma (SCC). Methods: We studied 283 patients with esophageal SCC who underwent ER. The study outcomes were as follows: (1) incidence of metachronous primary GC after ER; and (2) predictors for the development of metachronous primary GC after ER by the Cox proportional hazards model. Results: The median follow-up was 43.1 months (1.81–79.1), and the 3-year cumulative incidence of metachronous primary GC was 6.5% (95%CI: 4.1–10.4). The incidence of metachronous primary GC during the follow-up period was 2.31 per 100 person-years. The frequencies of severe gastric atrophy and macrocytosis at the timing of ER were significantly higher in patients with than without metachronous primary GC (91.7% vs. 73.2%, p = 0.0422, 20.8% vs. 5.2%, p = 0.0046, respectively). Severe gastric atrophy was associated with the development of metachronous primary GC (sex-and-age adjusted hazard ratio (HR) [95%CI] = 4.12 [0.95–27.78], p = 0.0093). Macrocytosis was associated with the development of metachronous primary GC (sex-and-age adjusted HR = 4.76 [1.75–13.0], p = 0.0012) and found to be an independent predictor for metachronous primary GC by multivariate Cox proportional hazards analysis (HR [95%CI] = 4.35 [1.60–11.84], p = 0.004). Conclusions: Severe gastric atrophy and macrocytosis should be noted in the development of metachronous primary GC after ER for esophageal SCC. In particular, macrocytosis at the timing of ER was considered an important predictor. Clinical trials registry number: UMIN000001676. [ABSTRACT FROM AUTHOR]

Purpose: Nivolumab is useful for the treatment of unresectable/recurrent gastric cancer as third-line or later chemotherapy. However, the factors that predict the efficacy of nivolumab monotherapy remain unclear. Methods: We retrospectively studied the predictive factors of response in 59 consecutive patients treated with nivolumab as third-line or later chemotherapy for unresectable/recurrent gastric cancer at our hospital from October 2017 to May 2020. Results: The median follow-up was 5.9 months. The study included 45 men and 14 women (median age: 71 years). We observed that 7 patients had an Eastern Cooperative Oncology Group performance status of 0 and 52 patients had a performance status of 1–2. Forty-three patients were treated with third-line therapy, seven with fourth-line therapy, and three with fifth-line therapy. The response rate to nivolumab was 6.7% and disease control rate was 35.5%. There were 19 (32.2%) immune-related adverse events for all grades and 9 (15.2%) for grades 3 and 4. Progression-free survival was 1.90 months, and overall survival was 6.30 months. Patients with immune-related adverse events had significantly longer overall survival than those without immune-related adverse events. Multivariate analysis showed that the occurrence of immune-related adverse events and a ratio for neutrophil-to-lymphocyte ratio after 8 weeks of nivolumab treatment to the baseline neutrophil-to-lymphocyte ratio before treatment of ≤ 1.5 were independent prognostic factors for overall survival. Conclusions: Occurrence of immune-related adverse events and changes in neutrophil-to-lymphocyte ratio during nivolumab treatment may help predict the therapeutic efficacy of nivolumab monotherapy for unresectable or recurrent gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Patients with early esophageal squamous cell carcinoma (ESCC) may develop multiple second primary ESCC and cancers in other organs even after curative endoscopic resection (ER). We investigated whether administration of chemoradiotherapy (CRT) after ER decreases the incidence of second primary cancers. Methods: We conducted a post hoc analysis of the prospective study. Among the registered 170 patients with clinical submucosal ESCC, 74 underwent ER alone, and 96 underwent ER followed by CRT (ER + CRT) because of pathological results of submucosal or lympho-vascular invasion. We compared the incidence of second primary cancers in esophagus and in other organs between two treatment groups. A univariate analysis was performed to investigate the related risk factors. All patients were followed up with esophagogastroduodenoscopy and CT every 4 months for the first 3 years and every 6 months thereafter. Results: Sixty-one ESCC were detected in 32 patients, and the 3-year cumulative incidence of multiple ESCCs was not different between ER + CRT and ER alone (10.4% vs. 13.5%). Sixty-three second primary cancers in other organs were detected in 45 patients, and there was no difference in the cumulative incidence between two groups. The risk factors for multiple ESCCs were high alcohol consumption and grade C multiple Lugol-voiding lesions. Heavy drinker or patients with grade C multiple Lugol-voiding lesion rather than CRT were at risk for second primary ESCC. Conclusion: CRT after ER did not decrease the cumulative incidence of second primary ESCC nor cancers in other organs comparing with ER alone. [ABSTRACT FROM AUTHOR]

Introduction: Direct comparison studies about the incidence of esophagogastric complications between radiofrequency (RF) and cryoballoon (CB) catheter ablation (CA) for atrial fibrillation (AF) have been scarce. We sought to elucidate the relationship between the pulmonary vein isolation (PVI) modalities and esophagogastric complications. Methods: The study population consisted of 254 patients who underwent CA for AF from November 2017 to October 2018. Finally, 160 patients were enrolled and divided into the RF and CB groups. Esophageal ulcers, gastric hypomotility, and exfoliative esophagitis detected by esophagogastroduodenoscopy were defined as esophagogastric complications in this study. Results: The median age was 68 years old, with 34% being females. Esophagogastric complications were observed in 42.5% of patients who underwent CA. According to the detailed esophagogastric complications, the RF group had a higher prevalence of esophageal ulcers than the CB group (19% vs. 0%, p <.0001). There was no significant difference between the two groups regarding gastric hypomotility and exfoliative esophagitis (18% vs. 28%; p =.15 and 16% vs. 21%; p =.42, respectively). Conclusion: Asymptomatic esophagogastric complications were common in CA for AF. The incidence of esophageal ulcers was higher in the RF group than in the CB group, whereas the other esophagogastric complications did not significantly differ. [ABSTRACT FROM AUTHOR]

Endoscopic Diagnosis of Esophageal and Pharyngeal Squamous Cell Carcinoma Esophageal cancer is the seventh most common cancer and the sixth most common cause of cancer-related mortality worldwide, with 572,000 new cases and 509,000 deaths in 2018.1 Esophageal squamous cell carcinoma (SCC) is the predominant subtype, accounting for 80% of esophageal cancers in the world and over 90% of esophageal cancers in Japan. Superficial esophageal cancer is an early-phase cancer defined as cancer limited to the mucosa or the submucosa. Applying this method to high-risk populations for esophageal cancer, e.g. heavy alcohol drinkers or patients with a history of pharyngeal cancer, realized efficient detection of superficial esophageal cancer. Pharyngeal cancer is the most common second cancer in patients with esophageal cancer. [Extracted from the article]

Superficial esophageal cancer is an early-phase cancer defined as cancer limited to the mucosa or the submucosa. Pharyngeal cancer is the most common second cancer in patients with esophageal cancer. Applying this method to high-risk populations for esophageal cancer, e.g. heavy alcohol drinkers or patients with a history of pharyngeal cancer, realized efficient detection of superficial esophageal cancer. Endoscopic Diagnosis of Esophageal and Pharyngeal Squamous Cell Carcinoma Esophageal cancer is the seventh most common cancer and the sixth most common cause of cancer-related mortality worldwide, with 572,000 new cases and 509,000 deaths in 2018.1 Esophageal squamous cell carcinoma (SCC) is the predominant subtype, accounting for 80% of esophageal cancers in the world and over 90% of esophageal cancers in Japan. [Extracted from the article]

Objectives: The Japan Endoscopy Database Project was initiated to develop the world's largest endoscopy data repository. This study describes the first phase of the colonoscopy project in Japan. Methods: Data were aggregated offline by integrating information from the endoscopy database software from January 2015 through March 2017. The study population included all patients who underwent colonoscopy at eight centers. Results: A total of 31,395 patients who underwent 38,497 colonoscopy procedures were registered. The majority of procedures were performed for screening (n = 14,156), followed by fecal immunochemical test positivity (n = 3960), abdominal symptoms (n = 3864), post‐colorectal surgery surveillance (n = 3431), post‐endoscopic treatment surveillance (n = 3757), thorough pre‐treatment examination (n = 2822), and therapeutic purposes (n = 6507). In the screening group, advanced cancers, early cancers, and adenomas were diagnosed endoscopically in 2.1%, 1.3%, and 28.7% of cases, respectively, while in the fecal immunochemical test‐positive group, they were diagnosed in 2.5%, 1.9%, and 41.6% of cases, respectively. The incidence of complications was 0.177% and 0.152% in the screening and fecal immunochemical test‐positive groups, respectively. The therapeutic procedures included 1446 cold forceps polypectomy procedures, 4770 cold snare polypectomy procedures, 368 hot biopsies, 2998 hot snare polypectomy procedures, 9775 endoscopic or piecemeal endoscopic mucosal resections, and 1660 endoscopic submucosal dissections. A total of 173 procedure‐related complications (0.82%) occurred in 21,017 therapeutic procedures performed in 15,744 patients. Conclusions: The first phase of the Japan Endoscopy Database Project established the proportions of the diagnostic and therapeutic colonoscopy procedures, and complication rates in real‐world settings. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative infectious complications have a negative impact on survival outcomes in patients with gastric cancer. It is recently reported that preoperative chemotherapy may eliminate this negative impact. This study aimed to confirm whether preoperative chemotherapy can eliminate the negative impact of postoperative infectious complications (IC) on survival outcomes and elucidate the association between postoperative infectious complications and recurrence patterns. Methods: We retrospectively reviewed data of 86 patients who received preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by R0 gastrectomy at the Kitasato University between 2006 and 2016. Patients who developed grade II or higher infectious complications during hospitalization were grouped into the IC group, while others were grouped into the non-IC (NIC) group. Survival outcomes and recurrence patterns were analyzed between the two groups. Results: Infectious complications with Clavien-Dindo classification of grade II or higher were found in 12 patients (14.0%, IC group). The median observational period was 61 months. Overall survival and progression-free survival were similar in the IC and NIC groups. Recurrence occurred in 39 patients. The proportions of peritoneal and lymph node recurrences were not significantly different between the two groups. However, the proportion of distant metastasis in the IC group was significantly higher than that in NIC group (3/4 [75%] vs. 9/35 [17%], p = 0.04). Conclusions: Pathological stage after neoadjuvant therapy plays a stronger role in recurrence than postoperative complications. Lymph node and peritoneal metastasis may be suppressed by preoperative chemotherapy. [ABSTRACT FROM AUTHOR]

Background: This randomized study was designed to evaluate the clinical effect of an elemental diet during chemotherapy in patients with esophageal cancer. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study.Methods: Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC.Results: 330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %.Conclusions: Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes. [ABSTRACT FROM AUTHOR]

A 76-year-old man had a diagnosis of double primary cancers consisting of poorly differentiated esophageal squamous cell carcinoma (ESCC) invading the submucosa and poorly differentiated gastric adenocarcinoma (GAC) invading the submucosa. The clinical stage of both ESCC and GAC was T1N0M0 stage I. The tumor diameter of ESCC and GAC was 20 mm and 25 mm, respectively. We performed chemoradiotherapy for ESCC. Chemotherapy consisted of nedaplatin in an intravenous dose of 90 mg/m2 on day 1 and 5-fluorouracil in an intravenous dose of 800 mg/m2 on days 1–5, repeated every 4 weeks for two cycles. Radiotherapy consisted of 50.4 Gy in 28 fractions for ESCC. GAC was down-staged after chemoradiotherapy for ESCC and was treated by endoscopic submucosal dissection (ESD). The tumor was histopathologically confirmed to be down-staged to intramucosal cancer with a diameter of 18 mm and no evidence of lymphovascular invasion and ulceration. Multiple metastasis occurred in the stomach, the small intestine and the colorectum after ESD. ESD is not a curative treatment even if chemotherapy is effective for poorly differentiated GAC invading the submucosa. Multiple gastrointestinal metastasis may be a unique recurrence pattern after ESD for such a lesion. [ABSTRACT FROM AUTHOR]

Purpose: With the widespread use of definitive chemoradiotherapy (dCRT) for esophageal squamous cell carcinoma (ESCC), salvage surgery for recurrence/residual patients became prevalent. However, survival impact of salvage surgery remains obscure at present. Methods: The updated clinical outcomes of salvage surgery were investigated to know its survival impact. Of the 155 ESCC patients who underwent dCRT between 2009 and 2016, we included 85 patients with recurrence or residual disease. The median follow-up was 65 months. Results: Of the 85 patients with progression disease, there were 42 and 43 patients of recurrence and residual disease, respectively. Salvage surgery was performed in 27 patients after dCRT, including 15 patients who underwent salvage esophagectomy. The 5-year overall survival (OS) of salvage surgery and otherwise patients was 66.1% and 14.5%, and the patients with salvage surgery had a significantly better prognosis (p < 0.0001). In the 15 patients who underwent salvage esophagectomy, residual disease, lymph node metastasis-positive (ycN+) after dCRT, and pathological lymph node metastasis-positive (ypN+) were significantly associated with poor prognosis (p = 0.0492, p = 0.0006, p = 0.0276), and the 5-year OS rates for the ycN/ypN combinations were 90%, 33.3%, and 0% in ycN−/ypN−, ycN+/ypN−, and ycN+/ypN+ patients, respectively (p = 0.0026). In a multivariate analysis, ycN+ was an independent poor prognostic factor (HR 13.6, 95% CI 1.65–286.8, p = 0.0154). Conclusions: Survival impact of salvage surgery after dCRT is robust, and lymph node metastasis after dCRT may help determine the indication for salvage esophagectomy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the long-term survival outcomes of KDOG1001 trial after a minimum follow-up of 3 years. Methods: Patients with bulky N2 lymph nodes, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) received up to four 28-day cycles of DCS neoadjuvant chemotherapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 lymphadenectomy plus adjuvant S-1 therapy for 1 year. The final preplanned analysis of long-term outcomes including overall survival and relapse-free survival was conducted after minimum follow-up of 3 years. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN 000003642, and has been completed. Results: From May 2010 through January 2017, 40 patients were enrolled. All included patients underwent neoadjuvant chemotherapy with DCS followed by gastrectomy with D2 lymphadenectomy, and 32 (80%) completed adjuvant S-1 therapy for 1 year. After a median follow-up for surviving patients of 68 months at the last follow-up in January 2020, 3-year overall survival rate was 77.5% (95% confidence interval 62.1–87.9%), while 3-year relapse-free survival rate was 62.5% (95% confidence interval 46.8–76.0%). Conclusion: Neoadjuvant chemotherapy with 4 cycles of DCS followed by D2 gastrectomy plus adjuvant S-1 was associated with relatively good long-term oncologic outcomes for patients with the high-risk gastric cancer. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the relation between dysplastic squamous epithelium in the esophageal mucosa and the development of metachronous secondary primary malignancies (mSPM) other than esophagus after endoscopic resection (ER) in patients with early esophageal squamous cell carcinoma (SCC). We studied 330 patients with early esophageal SCC who underwent ER as a post hoc analysis of a prospective multicenter cohort study (UMIN Clinical Trials Registry ID UMIN000001676). Lugol-voiding lesions (LVL) were graded into 3 categories (A = no lesion; B = 1 to 9 lesions; C ≥ 10 lesions). The following variables were studied: (i) the incidences of mSPM other than esophagus; (ii) the standardized incidence ratios (SIRs) of mSPM; (iii) the cumulative incidence and total number of mSPM other than esophagus; and (iv) predictors of mSPM other than esophagus on analysis with a multivariate Cox proportional-hazards model. After a median follow-up of 46.6 months, mSPM other than esophagus was diagnosed in a total of 73 patients (90 lesions). Among the 106 patients in group C, 37 patients had mSPM (51 lesions), including head and neck cancer in 14 patients (24 lesions) and gastric cancer in 12 patients (16 lesions). The SIR of mSPM was 3.61 in this study subjects. An increase in the LVL grade (A to B to C) was associated with a progressive increase in the cumulative incidence rate of mSPM other than esophagus (P  = 0.017 for A vs. C, P  = 0.023 for B vs. C). An increase in the LVL grade (A to B to C) was also associated with a progressive increase in the total number of mSPM other than esophagus per 100 person-years (primary events, relative risk [RR] = 1.66 and 3.24 for grades B and C, respectively, vs. A, P  = 0.002 for trend; all events, RR = 1.81 and 4.66 for grades B and C, respectively, vs. A, P  < 0.0001 for trend). LVL grade C was a strong predictor of mSPM other than esophagus (RR = 3.41 for A vs. C). LVL grade may be a useful predictor of the risk of mSPM other than esophagus after ER in patients with early esophageal SCC. [ABSTRACT FROM AUTHOR]

The diagnosis of Barrett's esophageal adenocarcinoma (BEA) in patients with Barrett's esophagus (BE) using endoscopy can be difficult and there are few specific endoscopic findings for BEA. However, white globe appearance (WGA) has been reported to be a specific endoscopic finding for early gastric cancer. We encountered a 51-year-old male patient with BEA exhibiting WGA. Esophagogastroduodenoscopy identified a red, depressed lesion of 10 mm within the long-segment BE (LSBE), while magnifying endoscopy with narrow-band imaging identified WGA. Endoscopic submucosal dissection (ESD) was performed based on our suspicion of BEA. Based on the ESD findings, we diagnosed adenocarcinoma accompanying LSBE histopathologically. WGA was identified, and intraglandular necrotic debris was discovered histologically at the same site. Therefore, WGA may be helpful in the diagnosis of BEA. [ABSTRACT FROM AUTHOR]

Follow-up studies of Japanese patients who had undergone endoscopic resection (ER) for early esophageal squamous cell carcinoma (ESCC) have reported a high prevalence of metachronous SCC in the upper aerodigestive tract (UAT). This prospective multicenter cohort study followed up 330 Japanese patients after ER of ESCC for a median of 49.4 months. The Alcohol Use Disorders Identification Test (AUDIT) for the 12-month period prior to study registration revealed high frequencies of high-risk drinking behaviors: 84 (25.4%) subjects had AUDIT scores of ≥15 points (suspected alcohol dependence) and 121 (36.7%) subjects had AUDIT scores of 8–14 points (hazardous drinking). Seventy-four subjects were metachronously diagnosed with ESCC, and 20 subjects with head and neck SCC (HNSCC). AUDIT scores ≥15 were associated with increases in the total number of HNSCCs per 100 person-years (0.4 for 0–7, 1.2 for 8–14 and 7.1 for ≥15; P < 0.0001). AUDIT scores were progressively associated with the grade of esophageal Lugol-voiding lesions (LVLs), a predictor of field cancerization in the UAT. Both an AUDIT score of ≥15 points and the presence of multiple LVLs were independent predictors of metachronous HNSCC [multivariate hazard ratio (95% confidence interval) = 6.98 (1.31–37.09) and 3.19 (1.19–8.54), respectively]. However, a high AUDIT score was not a predictor of metachronous ESCC. In conclusion, high AUDIT scores were markedly frequent in this population and increased the risk of metachronous HNSCC. The assessment of drinking behavior using the AUDIT and the completion of interventions for alcohol problems should be incorporated into the treatment strategy of ESCC. The name of the clinical trial register and the clinical trial registration number: Japan Esophageal Cohort Study, UMIN000001676. [ABSTRACT FROM AUTHOR]

Background: The optimal dose of each drug used in the docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy remains to be clarified for the Japanese population. The purpose of this study was to determine a recommended dose for a combination neoadjuvant DOS chemotherapy for Japanese patients with locally advanced adenocarcinoma of the esophagogastric junction (AEG). Methods: Patients with cT3 or more advanced AEG without distant metastasis were eligible for this study. The planned dosages of docetaxel (mg/m2, day 1), oxaliplatin (mg/m2, day 1), and S-1 (mg/day, days 1–14) were: 50/100/80–120 at level 1, and 60/100/80–120 at level 2, respectively. The treatment cycle was repeated every 3 weeks, and patients were assessed for response to the treatment after 2 and 3 cycles. This study was registered in the UMIN Clinical Trial Registry (UMIN 000022210). Results: We enrolled 12 patients with locally advanced AEG in this study. At dose level 1, one of the six patients experienced dose-limiting toxicity (DLT) of grade 3 diarrhea and grade 3 febrile neutropenia. Two of the next six patients also experienced DLT of need for more than 2-week delay of the start of the second cycle due to adverse events at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. Conclusion: Recommended doses of docetaxel (mg/m2), oxaliplatin (mg/m2), and S-1 (mg/day) were 60/100/80–120. This chemotherapy scheme showed good preliminary efficacy with acceptable toxicity warranting a further phase II trial to investigate the efficacy of this regimen. [ABSTRACT FROM AUTHOR]

Background and Aim: Few studies have reported on a national, population‐based endoscopic retrograde cholangiopancreatography (ERCP) database. Hence, in 2015, we established a multicenter ERCP database registry, the Japan Endoscopic Database (JED) Project in preparation for a nationwide endoscopic database. The objective the present study was to evaluate this registry before the establishment of a nationwide endoscopic database. Methods: From 1 January 2015 to 31 March 2017, we collected and analyzed the ERCP data of all patients who underwent ERCP in four participating centers in the JED Project based on the JED protocol. Results: Four centers carried out 4104 ERCP on 2173 patients. Data entry of ERCP information (age, 100%; gender, 100%; American Society of Anesthesiologists Physical Status Classification System, 74.5%; scope, 92.7%; time to ERCP, 100%; antithrombotic drug information, 55.0%; primary selective common bile duct [CBD] cannulation methods, 73.0%; number of attempts at primary selective CBD cannulation, 67.6%; overall selective CBD cannulation methods, 68.9%; ERCP procedure time, 66.3%; fluoroscopy time, 65.1%; adverse events, 74.9%; serum amylase levels 1 day post‐ERCP, 36.5%) was accurately extracted from the four centers. Success rate of CBD cannulation by level of ERCP difficulty was 98.5%, 99.0%, and 96.4% in grades 1, 2, and 3, respectively. Complication rate by overall selective CBD cannulation method was 5.6%, 7.6%, and 10.5% in the contrast‐assisted technique, guidewire‐assisted technique, and cross‐over method, respectively. Conclusion: Data from this evaluation of the JED Project, a multicenter ERCP database registry, suggest the feasibility of establishing a nationwide ERCP database and its challenges. [ABSTRACT FROM AUTHOR]

The Japan Gastroenterological Endoscopy Society has developed endoscopic submucosal dissection/endoscopic mucosal resection guidelines. These guidelines present recommendations in response to 18 clinical questions concerning the preoperative diagnosis, indications, resection methods, curability assessment, and surveillance of patients undergoing endoscopic resection for esophageal cancers based on a systematic review of the scientific literature. [ABSTRACT FROM AUTHOR]

Background: Standard treatment for resectable small cell neuroendocrine carcinoma of the esophagus (SCNEC-E) remains to be established. Methods: We retrospectively studied 7 consecutive patients with resectable SCNEC-E who received definitive chemoradiotherapy (dCRT) to evaluate the safety and efficacy. Treatment consisted of two courses of chemotherapy with cisplatin (80 mg/m2 on day 1) and etoposide (100 mg/m2 on days 1–3) or carboplatin (AUC 5 on day 1) and etoposide (80 mg/m2 on days 1–3) given every 4 weeks during dCRT. The total radiation dose was 50.4 Gy (28 fractions). Results: The clinical stage was IA in 1 patient, IB in 2 patients, IIA in 3 patients, and IIB in 1 patient. Definitive CRT was completed in all patients. The median overall treatment time of radiotherapy was 44 days. The chemotherapy regimen included in dCRT was cisplatin and etoposide in 3 patients and carboplatin and etoposide in 4 patients. Acute adverse events of grade 3 or 4 were neutropenia 100%, thrombocytopenia 43%, febrile neutropenia 43%, and nausea 14%. There were no late grade 3 or 4 adverse events. The median survival time was 32 months. The complete response rate was 100%. The recurrence rate was 43%. The median survival of the 4 patients without recurrence was 56 months. Conclusions: Definitive CRT with cisplatin and etoposide or carboplatin and etoposide is a feasible treatment for the resectable SCNEC-E, and long-term survival can be achieved in some patients. [ABSTRACT FROM AUTHOR]

Background: Macrocytosis is associated with an increased risk of squamous cell carcinoma (SCC) arising in the esophagus in men. The aim of this study was to evaluate the association between macrocytosis and metachronous SCC of the esophagus after endoscopic resection (ER) of early esophageal SCC in men. Methods: The study group comprised 278 men with early esophageal SCC after ER. The main study variables were as follows: (1) cumulative incidence and total number of metachronous SCC of the esophagus according to the presence or absence of macrocytosis (mean corpuscular volume ≥ 106 fl) and (2) predictors of metachronous SCC of the esophagus as assessed with a multivariate Cox proportional-hazards model. Results: The median follow-up was 50.3 months. Macrocytosis was associated with a higher 2-year cumulative incidence of metachronous SCC of the esophagus (without macrocytosis vs. with macrocytosis: 11.4% vs. 38.1%, p = 0.002). Macrocytosis was also associated with a higher total number of metachronous SCC of the esophagus per 100 person-years (without macrocytosis vs. with macrocytosis: 7.7 vs. 31.5 per 100 person-years, p < 0.0001). In addition, macrocytosis was a significant predictor of metachronous SCC of the esophagus on multivariate Cox proportional-hazards analysis (relative risk 2.23). Conclusion: Macrocytosis is a useful predictor of the risk of metachronous SCC of the esophagus after ER of early esophageal SCC in men. [ABSTRACT FROM AUTHOR]

Background: OBP-801 is a novel histone deacetylase inhibitor being developed as an anticancer drug. In this study, we explored genes to predict drug resistance in human cancer. Methods: OBP-801 resistance was assessed in 37 strains of human cancer cell lines. Expression microarrays harboring 54,675 genes were used to focus on candidate genes, which were validated for both functional and clinical relevance in esophageal squamous cell carcinoma (ESCC). Results: OBP-801 is sensitive to esophageal, gastric, and thyroid cancer, and resistant to some esophageal and colorectal cancers. We therefore used ESCC to explore genes. Comprehensive exploration focused on ΔNp63/SOX2, which were both genetically and epigenetically overexpressed in ESCC. Genomic amplifications of ΔNp63/SOX2 were tightly correlated each other (r = 0.81). Importantly, genomic amplification of ΔNp63/SOX2 in the resected tumors after neoadjuvant chemotherapy was significantly associated with histological grade of response (G1). Forced expression of either of these two genes did not induce each other, suggesting that their functional relevances were independent and showed robust drug resistance in OBP-801, as well as 5-fluorouracil. Furthermore, ΔNp63 could exert a potent oncogenic potential. RNA interference of ΔNp63 supported its oncological properties, as well as drug resistance. Conclusion: Comprehensive exploration of genes involved in anticancer drug residence could identify critical oncogenes of ΔNp63/SOX2 that would predict chemotherapy response in ESCC. [ABSTRACT FROM AUTHOR]

Background: In elderly patients with superficial esophageal squamous cell carcinoma (ESCC), the optimal treatment strategy after non-curative endoscopic submucosal dissection (ESD) remains unclear. We aimed to evaluate the validity of additional treatments after non-curative ESD and post-ESD survival predictors in elderly patients with ESCC.Methods: Elderly patients (age > 75 years) treated with ESD for ESCC between January 2010 and July 2014 at six tertiary referral hospitals in Japan were retrospectively investigated and stratified according to lymph node metastasis risk, based on histological findings (high-risk factors: positive lymphovascular invasion, submucosal invasion, and positive/indeterminate vertical margin) and post-ESD treatment strategy: group A (287 patients; low risk), group B (41 patients; high risk, without additional treatment), and group C (32 patients; high risk, with additional treatment). We evaluated 3- and 5-year overall survival and disease-specific survival, and prognostic factors for post-ESD survival.Results: At a median follow-up of 38, 40, and 49 months, respectively, there was 1 esophageal cancer-related death in group A, 1 in group B, and none in group C, whereas 22, 9, and 3 patients in groups A, B, and C died of other diseases. The groups differed significantly in overall survival (92.4%; 87.6%; 93.4%, p = 0.022), although not in disease-specific survival (99.4%; 96.3%; 100%, p = 0.217). On multivariate analysis, Charlson Comorbidity Index (CCI) ≥ 2 was the only independent risk factor for post-ESD death (hazard ratio 7.92; 95% confidence interval 3.42-18.3; p < 0.001).Conclusions: A follow-up strategy without additional treatment after ESD for ESCC may be acceptable in high-risk elderly patients, especially for CCI ≥ 2. [ABSTRACT FROM AUTHOR]

Aim: To clarify whether antithrombotic drugs affect diagnosis using the immunochemical faecal occult blood test -(iFOBT) of colorectal neoplasia. Methods: Using the Japan Endoscopy Database from 8 centres between 2015 and 2017, we analyzed data about patients who were iFOBT positive and had received direct oral anticoagulants (DOAC), warfarin, aspirin or thienopyridine. One-to-one matching-analogue propensity score weighted analyses were performed to compare the positive predictive value (PPV) of all neoplasms, invasive and non-invasive colorectal cancers and adenomas between drug users and non-users. All neoplasms included invasive and non-invasive colorectal cancer, and adenomas. Results: We analyzed 197 DOAC users and 196 non-users, 153 warfarin users and 153 non-users, 408 aspirin users and 415 non-users, and 97 thienopyridine users and 97 non-users. No significant differences were observed in the PPV for all neoplasms (56.67 vs. 50.43%), invasive cancer (4.32 vs. 3.53%), non-invasive cancer (15.58 vs. 15.56%) or adenoma (53.13 vs. 48.09%) between the DOAC user and non-user groups. No significant differences were observed in the PPV for all neoplasia, invasive and non-invasive cancer, or adenoma between warfarin, aspirin and thienopyridine use and non-users. Conclusions: DOAC, warfarin, aspirin and thienopyridine use did not decrease the PPVs of the iFOBT used to evaluate all colorectal neoplasia. [ABSTRACT FROM AUTHOR]

Background: We evaluated the accuracy of endoscopic findings observed by narrow band imaging (NBI) combined with magnifying gastrointestinal endoscopy (GIE) for the differential diagnosis of cancerous and noncancerous laryngeal lesions. Methods: A total of 166 vocal cord lesions for which good images were obtained on NBI with magnifying GIE were evaluated with respect to the following 6 variables: macroscopic type, tumor location, color, white coat, keratinization, and abnormal microvessels. Results: Multivariate analysis showed that white coat (odds ratio [OR], 2.95, P = 0.05), keratosis (OR, 3.14, P = 0.02) and abnormal microvessels (OR, 31.1, P < 0.0001) were significantly related to laryngeal cancer. In the diagnosis of laryngeal cancer, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of abnormal microvessels were 84.4%, 88.6%, 91%, 80.5%, and 86.1%, respectively. Conclusion: The abnormal microvessels on NBI combined with magnifying GIE are useful for the differential diagnosis of laryngeal lesions. [ABSTRACT FROM AUTHOR]

Purpose: Treatment strategies for superficial esophageal squamous cell carcinoma (S-ESCC) are determined mainly on the basis of the depth of invasion. We retrospectively studied the accuracy of the depth of tumor invasion, comprehensively assessed using the Japan Esophageal Society (JES) classification. Methods: The study group comprised 256 patients who underwent narrow band imaging (NBI) magnifying endoscopy, and endoscopic submucosal dissection for S-ESCC. The depth of invasion of S-ESCC was classified into three groups: EP/LPM, MM/SM1, and SM2. The following variables were studied retrospectively: (1) the diagnostic accuracy of non-magnifying white-light endoscopy, (2) the diagnostic accuracy of type B vessels, (3) the diagnostic accuracy of avascular area (AVA), (4) the diagnostic accuracy of the JES classification, and (5) the diagnostic accuracy of comprehensive diagnosis. The depth of invasion was assessed by white-light non-magnifying endoscopy, followed by NBI magnifying endoscopy. Results: The positive predictive value (PPV) of white-light non-magnifying endoscopy was 86% for EP/LPM, 53% MM/SM1, and 74% for SM2. The PPV of the diagnosis of type B vessels was 93% for EP/LPM, 62% for MM/SM1, and 74% for SM2. The PPV of the AVA diagnosis was 73% for EP/LPM, 89% for MM/SM1, and 100% for SM2. The PPV of diagnosis according to the JES classification was 93% for EP/LPM, 65% for MM/SM1, and 77% for SM2. The PPV of the comprehensive diagnosis was 94% for EP/LPM, 63%, for MM/SM1, and 75% for SM2. Conclusions: The additional use of NBI magnifying endoscopy can enhance the diagnostic accuracy of the depth of invasion in patients with S-ESCC. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with gastric cancer with bulky node metastasis, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) remains poor. We conducted a phase II study to evaluate the safety and efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 (DCS) for establishing a new treatment modality that improves prognosis. Methods: Patients received up to four 28-day cycles of DCS therapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 nodal dissection. S-1 chemotherapy was administered for 1 year after surgical resection. The primary endpoint was the percentage of complete resections of the primary tumor with clear margins (R0 resection). The planned sample size was 40; this was calculated based on an expected R0 rate of 85% and a threshold R0 rate of 65%, with a one-sided alpha of 5% and a power of 90%. Results: Between 2010 and 2017, 40 patients were enrolled. The R0 resection rate was 90%. The most common grade 3 or 4 adverse events during DCS therapy were leukocytopenia (27.5%), neutropenia (55.0%), and hyponatremia (22.5%). The most common grade 3 or 4 surgical morbidity was pancreatic fistula (12.5%); mortality was 0%. The pathological response rate was 57.5% with a grade 3 histological response rate of 8%. Conclusions: Neoadjuvant chemotherapy with DCS was feasible and showed a sufficient R0 resection rate. A future study with a sufficient follow-up period should confirm survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) has been performed in a high proportion of patients with superficial esophageal squamous-cell carcinoma. Endoscopic aspiration mucosectomy (EAM) is a more straightforward technique that is easier to perform. We retrospectively evaluated the safety and efficacy of EAM and ESD to clarify the advantages and disadvantages of each procedure.Methods: A total of 374 patients (423 lesions) who underwent endoscopic resection were retrospectively studied. The following variables were evaluated (1) procedure time and adverse events as safety, and (2) en bloc complete resection rate, local recurrence rate, lymph node recurrence rate, overall survival rate, and cause-specific survival rate as efficacy.Results: EAM was performed in 134 patients (149 lesions), and ESD was performed in 240 patients (274 lesions). The procedure times of EAM and ESD were 31.0 ± 22.4 and 85.7 ± 46.5 min (p < 0.001), respectively. The perforation rates were 0 and 6.2% (p = 0.002), respectively. The en bloc complete resection rates were 48.3 and 91.6% (p < 0.001), respectively. The local recurrence rates were 5.5 and 0% (p < 0.001), respectively. For lesions measuring less than 15 mm in diameter, EAM had a relatively good en bloc complete resection rate (EAM, 76.1% vs. ESD, 100%) and a significantly short procedure time (EAM, 25.2 ± 15.2 min vs. ESD, 62.7 ± 35.2 min; p < 0.001).Conclusions: ESD has a higher en bloc complete resection rate and a better local control rate than EAM. For lesions measuring less than 15 mm in diameter, EAM may be a treatment option. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to investigate the current status of esophageal endoscopy, including the evaluation of smoking and alcohol consumption, in Japan. Methods: A total of 47,441 patients who underwent 69,748 sessions of esophageal endoscopy were registered in the Japan Endoscopy Database between January 2015 and March 2017. The study variables were as follows: (1) methods for monitoring the esophagus and the time required for monitoring and (2) the status of smoking and alcohol consumption in patients with esophageal cancer and head and neck cancer. Results: Image-enhanced endoscopy was performed in 10.6%, Lugol chromoendoscopy in 4.1%, and magnifying endoscopy in 3.2%. The mean time required for gastrointestinal endoscopy was 10 min 58 s. The mean examination times in patients with or without monitoring of the head and neck were 10 min 51 s and 11 min 13 s, respectively. In 57.0% of the patients with esophageal cancer, the head and neck were monitored at the time of gastrointestinal endoscopy. The proportion of current smokers (esophageal cancer: 16.8–4.7%; head and neck cancer: 24.3–9.3%) and addicted drinkers (esophageal cancer: 52.3–40.8%; head and neck cancer: 50.2–47.3%) were lower at the second or subsequent endoscopy than at the initial endoscopy. Conclusions: The new strategy for esophageal endoscopy has led to an evolutionary change in Japan. The patients with esophageal cancer and head and neck cancer who underwent a second or subsequent endoscopy had lower incidences of smoking and alcohol consumption, although the incidences remained high. [ABSTRACT FROM AUTHOR]

Background: Very few studies have evaluated the effectiveness of oral proton-pump inhibitors for the prevention of bleeding after endoscopic submucosal dissection (ESD) for gastric tumors. The aim of our study was to establish the non-inferiority of lansoprazole orally disintegrating (OD) tablets to intravenous lansoprazole for the prevention of bleeding from artificial ulcers after ESD.Patients and Methods: Consecutive patients who underwent ESD for gastric tumors were randomly assigned to receive lansoprazole OD tablets (OD group) or intravenous lansoprazole (IV group). In the OD group, lansoprazole OD tablets (30 mg) were given orally once daily for 8 weeks (56 days), starting on the day before ESD. In the IV group, lansoprazole (30 mg) was given as a continuous intravenous infusion twice daily for 3 days, starting on the day before ESD, and lansoprazole OD tablets (30 mg) were given orally once daily on days 4-56. The primary endpoint was the incidence of bleeding events within 8 weeks after ESD.Results: Among 310 enrolled patients, 304 patients (152 in the OD group and 152 in the IV group) were included in the analysis. Endoscopic hemostasis was performed in 38 patients (19 in the OD group and 19 in the IV group). The incidence of bleeding events within 8 weeks after ESD did not differ significantly between the groups (p = 0.487). Endoscopic hemostasis was performed at second-look endoscopy in 17 patients (11.2%) in the OD group and 19 patients (12.5%) in the IV group (difference, 1.3 percentage points; 90% confidence interval, - 4.8-7.4%; non-inferiority, p < 0.001).Conclusions: The effectiveness of lansoprazole OD tablets for the prevention of bleeding from artificial ulcers after ESD was similar to that of intravenous lansoprazole. Lansoprazole OD tablets are thus considered a treatment option in patients who undergo ESD. [ABSTRACT FROM AUTHOR]

Nimotuzumab is a humanized anti‐epidermal growth factor receptor IgG1 monoclonal antibody. This phase I study assessed the tolerability, safety, efficacy, and pharmacokinetics of nimotuzumab in combination with chemoradiotherapy in Japanese patients with esophageal cancer. Patients with stage II, III, and IV esophageal cancer were enrolled. Patients were planned to receive nimotuzumab (level 1: 200 mg/wk for 25 weeks; or level 2: 400 mg/wk in the chemoradiation period, 400 mg biweekly in an additional chemotherapy period [8 weeks after the chemoradiation period] and a maintenance therapy period [after chemotherapy to 25 weeks]) combined with cisplatin (75 mg/m2 on day 1) and fluorouracil (1000 mg/m2 on days 1‐4) in the chemoradiation and additional chemotherapy periods. Radiotherapy was given concurrently at 50.4 Gy. A total of 10 patients were enrolled in level 1. Dose‐limiting toxicities were observed in 2 patients (grade 3 infection and renal disorder). Maximum‐tolerated dose was estimated to be at least 200 mg/wk and the dose was not escalated to level 2. The most common grade ≥3 toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatremia, and radiation esophagitis (30% each). Neither treatment‐related death nor grade ≥3 skin toxicity was observed in any patient. Complete response rate was 50%. Progression‐free survival was 13.9 months. One‐ and 3‐year survival rates were 75% and 37.5%, respectively. Immunogenicity was not reported in any patient. Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese patients with esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer treatment guidelines recommend additional surgery as the standard treatment for lesions for which endoscopic submucosal dissection (ESD) is not indicated. However, the incidence of lymph-node metastasis is low in most patients.Methods and Materials: The study comprised 231 patients (231 lesions) who underwent ESD for early gastric cancer (EGC) in our hospital from September 2002 through March 2015 and were found to have lesions for which endoscopic treatment is not indicated on histopathological evaluation after ESD. The patients were divided into the additional operation group and the follow-up group, and long-term outcomes were studied retrospectively. Risk factors for metastasis and recurrence were also studied (capture rate, 98.7%).Results: The median follow-up was 48 months. There were 174 men and 57 women with a median age of 72 years. The additional operation group comprised 118 patients, and the follow-up group comprised 113 patients. The rates of 5-year cause-specific survival and 5-year overall survival were significantly higher in the additional operation group (100 and 96.0%, respectively) than in the follow-up group (92.6 and 73.3%, respectively; p = 0.010, p < 0.001). In the follow-up group, 5 patients (4.4%) died of gastric cancer (p = 0.021). Among elderly patients 75 years or older, long-term outcomes did not differ significantly between the groups. Sixteen patients had metastasis or recurrence, and the presence of lymphatic involvement was an independent risk factor for metastasis, recurrence, or both (p = 0.003; odds ratio 10.594; 95% confidence interval 2.294-48.927).Conclusions: In patients with EGC who are confirmed to have lesions for which endoscopic treatment is not indicated on histopathological evaluation after ESD, additional surgery should be aggressively performed if the patient can tolerate such treatment. In elderly patients aged 75 years or older and patients with serious underlying diseases, follow-up observation was suggested to be one option in patients who give informed consent after receiving an explanation of the risk of recurrence. [ABSTRACT FROM AUTHOR]

The advent of electronic medical records brought image filing systems to many hospitals, as well as electronic endoscopic medical records. However, data integration among multiple different vendors has not yet been accomplished. We start the Japan Endoscopic Database ( JED) Project endorsed by Japan Gastroenterological Endoscopy Society ( JGES) from January 2015. The purposes of this project are as follows: (i) developing the world's largest endoscopic database generated from daily use of the reporting system; (ii) capturing the actual performance of endoscopic practice in Japan; and (iii) standardizing the terminology and fundamental items for registry of clinical studies. Moreover, the JED project has the potential to automatically collect data about adverse events, competency and evaluation of residents, and actual numbers of procedures on a nationwide scale, certification for the specialty board system, and so on. We believe that this design paper will be helpful not only for future nationwide research but also for international research ( UMIN000016093). [ABSTRACT FROM AUTHOR]

Background and Aim The Japan Endoscopy Database ( JED) Project was started to develop the world's largest endoscopic database, capture the actual performance of endoscopic practice, and standardize the terminology and fundamental items needed for a clinical and research registry. This paper presents a progress report on the first phase of this project undertaken at eight endoscopic centers in Japan. Methods The list of data items to be collected was drafted by the MSED-J (Minimal Standard Endoscopic Database) subcommittee. These items were aggregated offline by integrating data from two endoscopic filing systems between July 2015 and December 2015. The study population included all patients who underwent esophagogastroduodenoscopy or colonoscopy at all eight centers, patients who underwent enteroscopy at five of the eight centers, and patients who underwent endoscopic retrograde cholangiopancreatography ( ERCP) at four of the eight centers. Results Data collected in this phase included 61 070 endoscopic procedures, of which 40 475 were esophagogastroduodenoscopies, 215 were enteroscopies, 19 204 were colonoscopies, and 1176 were ERCPs. Frequencies of complications were 0.68% for esophagogastroduodenoscopy, 0% for enteroscopy, 0.43% for colonoscopy, and 13.34% for ERCP. In addition, we obtained various data including Helicobacter pylori infection status, past history of endoscopy in patients who underwent enteroscopy or colonoscopy, and degree of difficulty of ERCP, although the frequencies of reporting were sometimes low, with some items <20%. Conclusion Results of the first phase suggest that the JED project can provide vast quantities of useful data about endoscopic procedures. [ABSTRACT FROM AUTHOR]

Background/aims: Few studies have classified risk factors according to the onset time of bleeding after endoscopic submucosal dissection (post-ESD bleeding).Methods: We studied 1767 consecutive lesions in patients who underwent ESD for early gastric cancer from December 2006 through June 2016. Patients who had a remnant stomach or who had undergone reconstruction with a gastric tube were excluded. Post-ESD bleeding was classified into acute bleeding (0-5 days after ESD) and delayed bleeding (6 or more days after ESD), and the risk factors for each type of bleeding were compared.Results: Post-ESD bleeding occurred in 150 (8.5%) of 1767 lesions. Bleeding was acute in 129 lesions (7.3%) and delayed in 21 (1.2%). Acute post-ESD bleeding was frequently associated with lesions located in the distal stomach, expanded indications or non-indicated lesions, a specimen diameter of ≥40 mm, and antithrombotic therapy. Delayed post-ESD bleeding was often associated with lesions located in the proximal stomach, hemodialysis, and antithrombotic therapy. Among 334 lesions in patients who received antithrombotic therapy, post-ESD bleeding occurred in 47 lesions (14.1%). Independent risk factors for post-ESD bleeding were a specimen diameter of ≥40 mm and treatment with 2 or more antithrombotic agents.Conclusions: Acute post-ESD bleeding and delayed post-ESD bleeding were associated with different clinical characteristics. Antithrombotic therapy is a risk factor for post-ESD bleeding in both the acute and delayed phases. [ABSTRACT FROM AUTHOR]

Background: This study was designed to validate a health-risk appraisal (HRA) model for identifying Japanese men in specialized hospitals who were at high risk for esophageal cancer on the basis of their past and present facial flushing reactions after drinking alcohol, drinking and smoking status, and intake of vegetables and fruit. Methods: We prospectively studied men 50 years or older with no history of head and neck cancer or esophageal cancer who presented at Kitasato University Hospital to undergo endoscopic examination from January 2011 to March 2013. The subjects responded to an HRA questionnaire before examination. Results: Among the 164 patients enrolled, 157 were eligible for analysis. The median HRA score was 3 in patients aged 70-90 years and 6 in those aged 50 to 69 years. Early esophageal cancer was diagnosed on endoscopic examination in 3 subjects (1.9%, 3/157). Among 70 patients 70-90 years of age, 18 (25.7%, 18/70) had an HRA score of 7 or higher, and early esophageal cancer was detected in 2 (11.1%, 2/18) of these patients. Early esophageal cancer was not detected in 87 patients 50-69 years of age. Early esophageal cancer was detected in a 70-year-old patient with an HRA score of 2 who had no history of drinking alcohol or smoking. Conclusions: Our results suggest that an HRA questionnaire is useful for identifying persons 70 years or older who are at high risk for alcohol-related esophageal cancer in specialized hospitals. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption combined with inactive aldehyde dehydrogenase-2 (ALDH2) and the presence of multiple esophageal Lugol-voiding lesions (LVLs; dysplasia) are strong predictors for multiple development of esophageal squamous cell carcinoma (ESCC) in East Asians. We invented a health risk appraisal (HRA) model for predicting the risk of ESCC based on drinking, smoking, dietary habits, and alcohol flushing, i.e., past or present facial flushing after drinking a glass of beer, a surrogate marker for inactive ALDH2. Methods: Prospective follow-up examinations (median follow-up time, 50.3 months) were performed in 278 Japanese men after endoscopic mucosectomy for early ESCC (UMIN Clinical Trials Registry ID: UMIN000001676). Results: Sixty-four subjects developed metachronous ESCC. A receiver operating characteristic curve showed that HRA scores ≥12 best predicted the development of metachronous ESCC. The ESCC detection rate per 100 person-years was 9.8 in the high-HRA-score group (n = 104) and 4.5 in the low-HRA-score group (n = 174), and the risk of development of metachronous ESCC was higher in the high-HRA-score group than in the low-HRA-score group (adjusted hazard ratio: 2.00 [95% CI: 1.12–3.30]). Multiple LVLs was a very strong predictor of the development of metachronous SCC, but high HRA scores predicted it independently. The cumulative incidences of metachronous ESCC decreased after drinking cessation in the high-HRA-score drinker group (adjusted hazard ratio: 0.37 [0.14–0.97]). Conclusions: Both the HRA model that included alcohol flushing and the multiple LVL grade predicted the development of metachronous ESCC in Japanese men after endoscopic mucosectomy for ESCC. Drinking cessation in the high-HRA-score drinker group reduced the rate of metachronous ESCC. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (NAC) has become prevalent in esophageal squamous cell carcinoma (ESCC), but its long-term prognostic advantages remain unclear. The latest prognostic outcomes in clinical Stage (cStage) II/III ESCC with NAC were herein elucidated. Patients and Methods: NAC prior to curative treatment was done in 115 cStage II/III ESCC patients with either cisplatin (CDDP)/5-fluorouracil (5-FU; CF) (n = 41) or docetaxel/CDDP/5-FU (DCF) NAC (n = 74) between 2007 and 2013. Results: (1) Esophagectomy was finally performed in 35 of the 41 CF NAC cases and in 48 of the 74 DCF NAC cases. The preservation rate of the esophagus was higher in the DCF NAC than in the CF NAC (p = 0.018). (2) The overall survival was better in DCF NAC than in CF NAC (p = 0.071), and progression-free survivals were 58.3% with DCF and 30.5% with CF (p = 0.0060). DCF NAC was associated with fewer cases of progression than CF NAC (p = 0.0040), largely due to excellent control of the preoperative disease (p = 0.018) and postoperative lymph node recurrence (p = 0.014). Conclusion: DCF NAC in cStage II/III ESCC could have a great potential to achieve a better prognosis due to suppression of specific progression events with a higher preservation rate of the esophagus. [ABSTRACT FROM AUTHOR]